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File343 - Proteotoxic insults and synaptic dysfunction in the aging brain2015-062019-01

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2014
Location: BF-GMS
Title:
2014 Grants
Start date: 2015-01

Reference code: PT/FB/BL-2014-343
Location: BF-GMS
Title:
343 - Proteotoxic insults and synaptic dysfunction in the aging brain
Duration: 2015-06 - 2019-01
Researcher(s):
Cláudio Emanuel Moreira Gomes, Andreas Martin Grabrucker, Joana Margarida Lopes da Silva Cristóvão, Sónia Cristina Alves Dickson Leal Solano
Institution(s): FCiências.ID – Associação para a Investigação e Desenvolvimento de Ciências (Portugal); Neurocenter of Ulm University (Germany)
Contents: Contents:
Application form
Correspondence
Progress report
Final report
Articles
Author: Gomes, C.
Secondary author(s):
Grabrucker, A., Cristóvão, J., Solano, S.
Keywords:
Protein homeostasis / Brain biometals / Neuroinflammation / Synaptic Biochemistry / Psychophysiology

DocumentPreparation of amyloidogenic aggregates from EF-hand ß-parvalbumin and S100 proteins2018

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2014
Location: BF-GMS
Title:
2014 Grants
Start date: 2015-01

Reference code: PT/FB/BL-2014-343
Location: BF-GMS
Title:
343 - Proteotoxic insults and synaptic dysfunction in the aging brain
Duration: 2015-06 - 2019-01
Researcher(s):
Cláudio Emanuel Moreira Gomes, Andreas Martin Grabrucker, Joana Margarida Lopes da Silva Cristóvão, Sónia Cristina Alves Dickson Leal Solano
Institution(s): FCiências.ID – Associação para a Investigação e Desenvolvimento de Ciências (Portugal); Neurocenter of Ulm University (Germany)
Contents: Contents:
Application form
Correspondence
Progress report
Final report
Articles
Author: Gomes, C.
Secondary author(s):
Grabrucker, A., Cristóvão, J., Solano, S.
Keywords:
Protein homeostasis / Brain biometals / Neuroinflammation / Synaptic Biochemistry / Psychophysiology

Reference code: PT/FB/BL-2014-343.02
Location: BF-GMS
Title:
Preparation of amyloidogenic aggregates from EF-hand ß-parvalbumin and S100 proteins
Publication year: 2018
URL:
https://link.springer.com/protocol/10.1007/978-1-4939-7816-8_11
Abstract/Results: ABSTRACT:
Proteins containing EF-hand helix-loop-helix-binding motifs play essential roles in calcium homeostasis and signaling pathways. These proteins have considerable structural and functional diversity by virtue of their cation-binding properties, and occur as either Ca2+-bound or Ca2+-free states with distinct aggregation propensities. That is the case among ß-parvalbumins and S100 proteins, which under certain conditions undergo Ca2+-dependent self-assembly reactions with the formation of oligomers, amyloid-type aggregates and fibrils. These phenomena may be particularly relevant in human S100A6 protein and in fish Gad m 1 allergenic protein, which are implicated in human disease processes. Here, we describe detailed methods to generate and monitor the formation of amyloidogenic assemblies and aggregates of these two EF-hand proteins in vitro.
Accessibility: Document does not exist in file
Language:
eng
Author:
Martínez, J.
Secondary author(s):
Cristóvão, J. S., Sánchez, R., Gasset, M., Gomes, C. M.
Document type:
Book chapter
Reference:
Martínez, J., Cristóvão, J. S., Sánchez, R., Gasset, M., & Gomes C.M. (2018). Preparation of amyloidogenic aggregates from EF-hand ß-parvalbumin and S100 proteins. In Sigurdsson E., Calero M., Gasset M. (Eds), Amyloid Proteins (pp. 167-179). New York, NY: Humana Press.
Indexed document: No
Keywords: Calcium / S100A6 / Gad m 1 / Fish allergens / Amyloids / EF-hand

DocumentZinc binding to S100B affords regulation of trace metal homeostasis and excitotoxicity in the brain2018

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2014
Location: BF-GMS
Title:
2014 Grants
Start date: 2015-01

Reference code: PT/FB/BL-2014-343
Location: BF-GMS
Title:
343 - Proteotoxic insults and synaptic dysfunction in the aging brain
Duration: 2015-06 - 2019-01
Researcher(s):
Cláudio Emanuel Moreira Gomes, Andreas Martin Grabrucker, Joana Margarida Lopes da Silva Cristóvão, Sónia Cristina Alves Dickson Leal Solano
Institution(s): FCiências.ID – Associação para a Investigação e Desenvolvimento de Ciências (Portugal); Neurocenter of Ulm University (Germany)
Contents: Contents:
Application form
Correspondence
Progress report
Final report
Articles
Author: Gomes, C.
Secondary author(s):
Grabrucker, A., Cristóvão, J., Solano, S.
Keywords:
Protein homeostasis / Brain biometals / Neuroinflammation / Synaptic Biochemistry / Psychophysiology

Reference code: PT/FB/BL-2014-343.03
Location: BF-GMS
Title:
Zinc binding to S100B affords regulation of trace metal homeostasis and excitotoxicity in the brain
Publication year: 2018
URL:
https://www.frontiersin.org/articles/10.3389/fnmol.2017.00456/full
Abstract/Results: ABSTRACT:
Neuronal metal ions such as zinc are essential for brain function. In particular synaptic processes are tightly related to metal and protein homeostasis, for example through extracellular metal-binding proteins. One such protein is neuronal S100B, a calcium and zinc binding damage-associated molecular pattern (DAMP), whose chronic upregulation is associated with aging, Alzheimer’s disease (AD), motor neuron disease and traumatic brain injury (TBI). Despite gained insights on the structure of S100B, it remains unclear how its calcium and zinc binding properties regulate its function on cellular level. Here we report a novel role of S100B in trace metal homeostasis, in particular the regulation of zinc levels in the brain. Our results show that S100B at increased extracellular levels is not toxic, persists at high levels, and is taken up into neurons, as shown by cell culture and biochemical analysis. Combining protein bioimaging and zinc quantitation, along with a zinc-binding impaired S100B variant, we conclude that S100B effectively scavenges zinc ions through specific binding, resulting in a redistribution of the intracellular zinc pool. Our results indicate that scavenging of zinc by increased levels of S100B affects calcium levels in vitro. Thereby S100B is able to mediate the cross talk between calcium and zinc homeostasis. Further, we investigated a possible new neuro-protective role of S100B in excitotoxicity via its effects on calcium and zinc homeostasis. Exposure of cells to zinc-S100B but not the zinc-binding impaired S100B results in an inhibition of excitotoxicity. We conclude that in addition to its known functions, S100B acts as sensor and regulator of elevated zinc levels in the brain and this metal-buffering activity is tied to a neuroprotective role.
Accessibility: Document exists in file
Language:
eng
Author:
Hagmeyer, S.
Secondary author(s):
Cristóvão, J. S., Mulvihill, J. E., Boeckers, T. M., Gomes, C. M., Grabrucker, A. M.
Document type:
Article
Reference:
Hagmeyer, S., Cristóvão, J. S., Mulvihill, J. E., Boeckers, T., Gomes, C., & Grabrucker, A. (2018). Zinc Binding to S100B Affords Regulation of Trace Metal Homeostasis and Excitotoxicity in the Brain. Frontiers in Molecular Neuroscience, 10: 456. 10.3389/fnmol.2017.00456
2-year Impact Factor: 3.720|2018
Times cited: 3|2019-07-11
Indexed document: Yes
Quartile: Q2
Keywords: Zn / Zinc / S100B / DAMP / Synapse / Calcium / Excitotoxicity / Zinc sensor

Zinc binding to S100B affords regulation of trace metal homeostasis and excitotoxicity in the brain

Zinc binding to S100B affords regulation of trace metal homeostasis and excitotoxicity in the brain

DocumentThe neuronal S100B protein is a calcium-tuned suppressor of amyloid-b aggregation2018

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2014
Location: BF-GMS
Title:
2014 Grants
Start date: 2015-01

Reference code: PT/FB/BL-2014-343
Location: BF-GMS
Title:
343 - Proteotoxic insults and synaptic dysfunction in the aging brain
Duration: 2015-06 - 2019-01
Researcher(s):
Cláudio Emanuel Moreira Gomes, Andreas Martin Grabrucker, Joana Margarida Lopes da Silva Cristóvão, Sónia Cristina Alves Dickson Leal Solano
Institution(s): FCiências.ID – Associação para a Investigação e Desenvolvimento de Ciências (Portugal); Neurocenter of Ulm University (Germany)
Contents: Contents:
Application form
Correspondence
Progress report
Final report
Articles
Author: Gomes, C.
Secondary author(s):
Grabrucker, A., Cristóvão, J., Solano, S.
Keywords:
Protein homeostasis / Brain biometals / Neuroinflammation / Synaptic Biochemistry / Psychophysiology

Reference code: PT/FB/BL-2014-343.04
Location: BF-GMS
Title:
The neuronal S100B protein is a calcium-tuned suppressor of amyloid-b aggregation
Publication year: 2018
URL:
http://advances.sciencemag.org/content/4/6/eaaq1702.full
Abstract/Results: ABSTRACT:
Amyloid-ß (Aß) aggregation and neuroinflammation are consistent features in Alzheimer’s disease (AD) and strong candidates for the initiation of neurodegeneration. S100B is one of the most abundant proinflammatory proteins that is chronically up-regulated in AD and is found associated with senile plaques. This recognized biomarker for brain distress may, thus, play roles in amyloid aggregation which remain to be determined. We report a novel role for the neuronal S100B protein as suppressor of Aß42 aggregation and toxicity. We determined the structural details of the interaction between monomeric Aß42 and S100B, which is favored by calcium binding to S100B, possibly involving conformational switching of disordered Aß42 into an a-helical conformer, which locks aggregation. From nuclear magnetic resonance experiments, we show that this dynamic interaction occurs at a promiscuous peptide-binding region within the interfacial cleft of the S100B homodimer. This physical interaction is coupled to a functional role in the inhibition of Aß42 aggregation and toxicity and is tuned by calcium binding to S100B. S100B delays the onset of Aß42 aggregation by interacting with Aß42 monomers inhibiting primary nucleation, and the calcium-bound state substantially affects secondary nucleation by inhibiting fibril surface–catalyzed reactions through S100B binding to growing Aß42 oligomers and fibrils. S100B protects cells from Aß42-mediated toxicity, rescuing cell viability and decreasing apoptosis induced by Aß42 in cell cultures. Together, our findings suggest that molecular targeting of S100B could be translated into development of novel approaches to ameliorate AD neurodegeneration.
Accessibility: Document exists in file
Copyright/Reproduction:
By permission
Language:
eng
Author:
Cristóvão, J. S.
Secondary author(s):
Morris, V. K., Cardoso, I., Leal, S., Martínez, J., Botelho, H. M., Göbl, C., David, R., Kierdorf, K., Alemi, M., Madl, T., Fritz, G., Reif, B., Gomes, C. M.
Document type:
Article
Reference:
Cristóvão, J. S., Morris, V. K., Cardoso, I., Leal, S., Martínez, J., Botelho, H. M., Göbl, C., David, R., Kierdorf, K., Alemi, M., Madl, T., Fritz, G., Reif, B., & Gomes, C. M. (2018). The neuronal S100B protein is a calcium-tuned suppressor of amyloid-B aggregation. Science Advances, 4(6), eaaq1702. doi: 10.1126/sciadv.aaq1702
2-year Impact Factor: 12.804|2018
Times cited: 3|2019-07-11
Indexed document: Yes
Quartile: Q1
Keywords: S100B / Calcium

The neuronal S100B protein is a calcium-tuned suppressor of amyloid-b aggregation

The neuronal S100B protein is a calcium-tuned suppressor of amyloid-b aggregation

DocumentFinal report - Proteotoxic insults and synaptic dysfunction in the aging brain2019

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2014
Location: BF-GMS
Title:
2014 Grants
Start date: 2015-01

Reference code: PT/FB/BL-2014-343
Location: BF-GMS
Title:
343 - Proteotoxic insults and synaptic dysfunction in the aging brain
Duration: 2015-06 - 2019-01
Researcher(s):
Cláudio Emanuel Moreira Gomes, Andreas Martin Grabrucker, Joana Margarida Lopes da Silva Cristóvão, Sónia Cristina Alves Dickson Leal Solano
Institution(s): FCiências.ID – Associação para a Investigação e Desenvolvimento de Ciências (Portugal); Neurocenter of Ulm University (Germany)
Contents: Contents:
Application form
Correspondence
Progress report
Final report
Articles
Author: Gomes, C.
Secondary author(s):
Grabrucker, A., Cristóvão, J., Solano, S.
Keywords:
Protein homeostasis / Brain biometals / Neuroinflammation / Synaptic Biochemistry / Psychophysiology

Reference code: PT/FB/BL-2014-343.01
Location: BF-GMS
Title:
Final report - Proteotoxic insults and synaptic dysfunction in the aging brain
Publication year: 2019
Abstract/Results:
ABSTRACT:
This project sought to investigate the hypothesis that age-related altered metallostasis and neuroinflammation-related proteotoxic seeds induce changes in synaptic protein networks that are critical to neuronal function. For this we studied mechanisms through which pro-inflammatory S100 proteins modulate synaptic processes, related to metal ion homeostasis and proteotoxic insults.
We demonstrated that inflammatory S100 proteins influence metal ion homeostasis at the synapse. We showed that extracellular levels of S100B are not toxic and are taken up by neurons. We proved that S100B, either expressed in cells or added extracellular, scavenges zinc ions through specific binding resulting in a redistribution of the intracellular zinc pool. Then we gather evidence that increased neuronal S100B only significantly affects calcium levels upon zinc scavenging in vitro. This led to the proposal of a new role of S100B as a neuro-protective mediator acting on excitotoxicity via its effects on calcium and zinc homeostasis. Indeed, we established that zinc binding to S100B mediates anti-excitotoxic activity effects.
We also characterized protein interactions between S100B and neuronal aggregation-prone proteins. We demonstrated that monomeric Aß42 interacts preferentially with calcium-bound S100B and pinpointed the interaction at promiscuous peptide-binding region within the interfacial cleft of the protein. We showed that this results in a delay of aggregation and in a decrease in the toxicity to neuroblastoma derived cell cultures. This resulted in a clear demonstration of a relationship between protein aggregation and inflammatory processes that take place in the synaptic milieu and are critical to neuronal function.
Accessibility: Document exists in file
Language:
eng
Author:
Gomes, C.
Secondary author(s):
Cristóvão, J., Martinez, J., Leal, S., Romão, M., David, R., Hagmeyer, S., Grabrucker, A.
Document type:
Final report
Reference:
Gomes, C., Cristóvão, J., Martinez, J., Leal, S., Romão, M., David, R., Hagmeyer, S., & Grabrucker, A. (2019). Final report - Proteotoxic insults and synaptic dysfunction in the aging brain
Indexed document: No
Keywords: Synaptic biochemistry / Brain proteostasis / Neurometals / Neurodegeneration / Neuroinflammation

Final report - Proteotoxic insults and synaptic dysfunction in the aging brain

Final report - Proteotoxic insults and synaptic dysfunction in the aging brain

DocumentSynthesis and effects of flavonoid structure variation on amyloid-ß aggregation2017

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2014
Location: BF-GMS
Title:
2014 Grants
Start date: 2015-01

Reference code: PT/FB/BL-2014-343
Location: BF-GMS
Title:
343 - Proteotoxic insults and synaptic dysfunction in the aging brain
Duration: 2015-06 - 2019-01
Researcher(s):
Cláudio Emanuel Moreira Gomes, Andreas Martin Grabrucker, Joana Margarida Lopes da Silva Cristóvão, Sónia Cristina Alves Dickson Leal Solano
Institution(s): FCiências.ID – Associação para a Investigação e Desenvolvimento de Ciências (Portugal); Neurocenter of Ulm University (Germany)
Contents: Contents:
Application form
Correspondence
Progress report
Final report
Articles
Author: Gomes, C.
Secondary author(s):
Grabrucker, A., Cristóvão, J., Solano, S.
Keywords:
Protein homeostasis / Brain biometals / Neuroinflammation / Synaptic Biochemistry / Psychophysiology

Reference code: PT/FB/BL-2014-343.05
Location: BF-GMS
Title:
Synthesis and effects of flavonoid structure variation on amyloid-ß aggregation
Publication year: 2017
URL:
https://www.degruyter.com/view/j/pac.2017.89.issue-9/pac-2017-0201/pac-2017-0201.xml
Abstract/Results: ABSTRACT:
Dietary flavonoids and synthetic derivatives have a well-known potential for biomedical applications. In this perspective, we report herein new methodologies to access chrysin and 5,7-dihydroxychromone, and these structures were combined with those of naturally occurring quercetin, luteolin, (+)-dihydroquercetin and apigenin to assemble a set of polyphenols with structure variations for in vitro testing over the aggregation of Alzheimer’s disease (AD) amyloid peptide Aß1-42. Using thioflavin-T (ThT) monitored kinetics and subsequent mechanistic analysis by curve fitting, we show that catechol-type flavonoids reduce Aß1-42 fibril content by 30% at molar ratios over 10. Without affecting secondary nucleation, these compounds accelerate primary nucleation events responsible for early primary oligomer formation, putatively redirecting the latter into off-pathway aggregates. Atomic force microscopy (AFM) imaging of reaction end-points allowed a comprehensive topographical analysis of amyloid aggregate populations formed in the presence of each compound. Formation of Aß1-42 small oligomers, regarded as the most toxic amyloid structures, seems to be limited by flavonoids with a C2 phenyl group, while flavonol 3-OH is not a beneficial structural feature. Overall, the diversity of structural variations within flavonoids opens avenues for their development as chemical tools in the treatment of AD by tackling the formation and distribution of neurotoxic oligomers species.
Accessibility: Document does not exist in file
Language:
eng
Author:
Matos, A. M.
Secondary author(s):
Cristóvão, J. S., Yashunsky, D. V., Nifantiev, N. E., Viana, A. S., Gomes, C. M., Rauter, A. P.
Document type:
Article
Reference:
Matos, A. M., Cristóvão, J. S., Yashunsky, D. V., Nifantiev, N. E., Viana, A. S., Gomes, C. M., Rauter, A. P. (2017). Synthesis and effects of flavonoid structure variation on amyloid-ß aggregation. Pure and Applied Chemistry, 89(9). doi: 10.1515/pac-2017-0201
2-year Impact Factor: 2.350|2018
Impact factor notes: Impact factor not available yet for 2019
Times cited: 1|2019-07-11
Indexed document: Yes
Quartile: Q1
Keywords: Amyloid-ß aggregation kinetics / Atomic force microscopy / Chemical synthesis / Flavonoids / ICS-28 / ThT fluorescence assay

DocumentMetals and neuronal metal binding proteins implicated in Alzheimer's Disease2016

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2014
Location: BF-GMS
Title:
2014 Grants
Start date: 2015-01

Reference code: PT/FB/BL-2014-343
Location: BF-GMS
Title:
343 - Proteotoxic insults and synaptic dysfunction in the aging brain
Duration: 2015-06 - 2019-01
Researcher(s):
Cláudio Emanuel Moreira Gomes, Andreas Martin Grabrucker, Joana Margarida Lopes da Silva Cristóvão, Sónia Cristina Alves Dickson Leal Solano
Institution(s): FCiências.ID – Associação para a Investigação e Desenvolvimento de Ciências (Portugal); Neurocenter of Ulm University (Germany)
Contents: Contents:
Application form
Correspondence
Progress report
Final report
Articles
Author: Gomes, C.
Secondary author(s):
Grabrucker, A., Cristóvão, J., Solano, S.
Keywords:
Protein homeostasis / Brain biometals / Neuroinflammation / Synaptic Biochemistry / Psychophysiology

Reference code: PT/FB/BL-2014-343.06
Location: BF-GMS
Title:
Metals and neuronal metal binding proteins implicated in Alzheimer's Disease
Publication year: 2016
URL:
Oxidative Medicine and Cellular Longevity
Abstract/Results: ABSTRACT:
Alzheimer’s disease (AD) is the most prevalent age-related dementia affecting millions of people worldwide. Its main pathological hallmark feature is the formation of insoluble protein deposits of amyloid-ß and hyperphosphorylated tau protein into extracellular plaques and intracellular neurofibrillary tangles, respectively. Many of the mechanistic details of this process remain unknown, but a well-established consequence of protein aggregation is synapse dysfunction and neuronal loss in the AD brain. Different pathways including mitochondrial dysfunction, oxidative stress, inflammation, and metal metabolism have been suggested to be implicated in this process. In particular, a body of evidence suggests that neuronal metal ions such as copper, zinc, and iron play important roles in brain function in health and disease states and altered homeostasis and distribution as a common feature across different neurodegenerative diseases and aging. In this focused review, we overview neuronal proteins that are involved in AD and whose metal binding properties may underlie important biochemical and regulatory processes occurring in the brain during the AD pathophysiological process.
Accessibility: Document exists in file
Language:
eng
Author:
Cristóvão, J. S.
Secondary author(s):
Santos, R., Gomes, C. M.
Document type:
Article
Reference:
Cristóvão, J. S., Santos, R., & Gomes, C. M. (2016). Metals and neuronal metal binding proteins implicated in Alzheimer's Disease. Oxidative Medicine and Cellular Longevity, Article ID 9812178. doi: 10.1155/2016/9812178
2-year Impact Factor: 4.868|2018
Times cited: 31|2019-07-11
Indexed document: Yes
Quartile: Q2
Keywords: Alzheimer's disease

Metals and neuronal metal binding proteins implicated in Alzheimer's Disease

Metals and neuronal metal binding proteins implicated in Alzheimer's Disease

DocumentBiophysical and spectroscopic methods for monitoring protein misfolding and amyloid aggregation2019

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2014
Location: BF-GMS
Title:
2014 Grants
Start date: 2015-01

Reference code: PT/FB/BL-2014-343
Location: BF-GMS
Title:
343 - Proteotoxic insults and synaptic dysfunction in the aging brain
Duration: 2015-06 - 2019-01
Researcher(s):
Cláudio Emanuel Moreira Gomes, Andreas Martin Grabrucker, Joana Margarida Lopes da Silva Cristóvão, Sónia Cristina Alves Dickson Leal Solano
Institution(s): FCiências.ID – Associação para a Investigação e Desenvolvimento de Ciências (Portugal); Neurocenter of Ulm University (Germany)
Contents: Contents:
Application form
Correspondence
Progress report
Final report
Articles
Author: Gomes, C.
Secondary author(s):
Grabrucker, A., Cristóvão, J., Solano, S.
Keywords:
Protein homeostasis / Brain biometals / Neuroinflammation / Synaptic Biochemistry / Psychophysiology

Reference code: PT/FB/BL-2014-343.06
Location: BF-GMS
Title:
Biophysical and spectroscopic methods for monitoring protein misfolding and amyloid aggregation
Publication year: 2019
URL:
https://link.springer.com/protocol/10.1007%2F978-1-4939-8820-4_1#citeas
Abstract/Results: ABSTRACT:
Proteins exhibit a remarkable structural plasticity and may undergo conformational changes resulting in protein misfolding both in a biological context and upon perturbing physiopathological conditions. Such nonfunctional protein conformers, including misfolded states and aggregates, are often associated to protein folding diseases. Understanding the biology of protein folding diseases thus requires tools that allow the structural characterization of nonnative conformations of proteins and their interconversions. Here we present detailed procedures to monitor protein conformational changes and aggregation based on spectroscopic and biophysical methods that include circular dichroism, ATR-Fourier-transformed infrared spectroscopy, fluorescence spectroscopy and dynamic light scattering. To illustrate the application of these methods we report to our previous studies on misfolding, aggregation and amyloid fibril formation by superoxide dismutase 1 (SOD1), a protein whose toxic deposition is implicated in the neurodegenerative disease amyotrophic lateral sclerosis (ALS).
Accessibility: Document does not exist in file
Language:
eng
Author:
Cristóvão, J. S.
Secondary author(s):
Henriques, B. J., Gomes, C. M.
Document type:
Book chapter
Reference:
Cristóvão, J. S., Henriques, B. J., & Gomes, C. M. (2019). Biophysical and spectroscopic methods for monitoring protein misfolding and amyloid aggregation. In C. Gomes (Eds.), Protein Misfolding Diseases. Methods in Molecular Biology (vol 1873, pp. 3-18). New York, NY: Humana Press. doi: 10.1007/978-1-4939-8820-4_1
Indexed document: Yes
Keywords: Circular dichroism / Fourier-transformed infrared spectroscopy / Fluorescence / Dynamic light scattering / Protein misfolding / Amyloid / Protein aggregation / Thioflavin T / SOD1 / ALS

DocumentBiophysical characterization of nanobody: Protein interactions relevant in Alzheimer’s disease2018

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2014
Location: BF-GMS
Title:
2014 Grants
Start date: 2015-01

Reference code: PT/FB/BL-2014-343
Location: BF-GMS
Title:
343 - Proteotoxic insults and synaptic dysfunction in the aging brain
Duration: 2015-06 - 2019-01
Researcher(s):
Cláudio Emanuel Moreira Gomes, Andreas Martin Grabrucker, Joana Margarida Lopes da Silva Cristóvão, Sónia Cristina Alves Dickson Leal Solano
Institution(s): FCiências.ID – Associação para a Investigação e Desenvolvimento de Ciências (Portugal); Neurocenter of Ulm University (Germany)
Contents: Contents:
Application form
Correspondence
Progress report
Final report
Articles
Author: Gomes, C.
Secondary author(s):
Grabrucker, A., Cristóvão, J., Solano, S.
Keywords:
Protein homeostasis / Brain biometals / Neuroinflammation / Synaptic Biochemistry / Psychophysiology

Reference code: PT/FB/BL-2014-343.08
Location: BF-GMS
Title:
Biophysical characterization of nanobody: Protein interactions relevant in Alzheimer’s disease
Publication year: 2018
URL:
http://www.itqb.unl.pt/meetings-and-courses/pcisbio/program-1/cristovao-et-al-pcisbio-day-abstract-2018.pdf
Abstract/Results: ABSTRACT:
S100B protein is one of the most abundant pro-inflammatory proteins which is chronically up-regulated in Alzheimer’s disease (AD) and is found within senile plaques [1]. Moreover, S100B is engaged in several processes linked with AD: regulates APP levels and generation of Aß peptides, interferes with tau protein phosphorylation and is involved in several AD-related signaling pathways. Recently we found that S100B binds to amyloid-ß peptide (Aß42) monomers and fibrils and acts as a suppressor of amyloid-ß peptide aggregation and toxicity [2]. Our finding raised the need to develop molecules that target S100B as a novel approach to ameliorate AD neurodegeneration. To fill this gap, we developed and purified a library of 24 single domain antibodies (nanobodies) targeting S100B protein in order to develop biological tools to stabilize the S100B:Aß42 complex. In most cases, the nanobody:S100B interaction occurs spontaneously, being favored by enthalpic forces. As determined by microscale thermophoresis (MST) and isothermal titration calorimetry (ITC), the binding affinity of nanobody:S100B interactions varies from high to low affinity (Kd=6-3000 nM) and the stoichiometry varies from 1 to 2 nanobodies per S100B protein. We found one nanobody that potentiates the inhibitory effect of S100B over Aß42 aggregation, promoting a strong suppression of Aß42 fibrillation, probably by stabilizing the S100B:Aß42 interaction. These newly developed nanobodies open new avenues to study other protein-protein interactions involving S100B on relevant disease processes.
Accessibility: Document exists in file
Language:
eng
Author:
Cristóvão, J. S.
Secondary author(s):
Birck, C., Pardon, E., Steyaert, J., Gomes, C. M.
Document type:
Online abstract
Reference:
Cristóvão, J.S., Birck, C., Pardon, E., Steyaert, J., & Gomes, C. M. (2018). Biophysical characterization of nanobody: Protein interactions relevant in Alzheimer’s disease. Paper presented ath the PCISBIO Day, Oeiras, Portugal. Abstract retrieved at http://www.itqb.unl.pt/meetings-and-courses/pcisbio/program-1/cristovao-et-al-pcisbio-day-abstract-2018.pdf
Indexed document: No
Keywords: Alzheimer's disease / Nanobody

Biophysical characterization of nanobody: Protein interactions relevant in Alzheimer’s disease

Biophysical characterization of nanobody: Protein interactions relevant in Alzheimer’s disease

DocumentDeveloping nanobodies to manipulate protein:protein interaction in neurodegenerative diseases2016

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2014
Location: BF-GMS
Title:
2014 Grants
Start date: 2015-01

Reference code: PT/FB/BL-2014-343
Location: BF-GMS
Title:
343 - Proteotoxic insults and synaptic dysfunction in the aging brain
Duration: 2015-06 - 2019-01
Researcher(s):
Cláudio Emanuel Moreira Gomes, Andreas Martin Grabrucker, Joana Margarida Lopes da Silva Cristóvão, Sónia Cristina Alves Dickson Leal Solano
Institution(s): FCiências.ID – Associação para a Investigação e Desenvolvimento de Ciências (Portugal); Neurocenter of Ulm University (Germany)
Contents: Contents:
Application form
Correspondence
Progress report
Final report
Articles
Author: Gomes, C.
Secondary author(s):
Grabrucker, A., Cristóvão, J., Solano, S.
Keywords:
Protein homeostasis / Brain biometals / Neuroinflammation / Synaptic Biochemistry / Psychophysiology

Reference code: PT/FB/BL-2014-343.09
Location: BF-GMS
Title:
Developing nanobodies to manipulate protein:protein interaction in neurodegenerative diseases
Publication year: 2016
URL:
http://www.itqb.unl.pt/meetings-and-courses/pcisbio/program-1/abstractsjcristovao.pdf
Abstract/Results: ABSTRACT:
Insoluble ß-amyloid peptide (Aß) deposits formed in the synaptic milieu, chronic activation of glial cells and inflammation are consistent features in Alzheimer’s disease (AD) and strong candidates for the initiation of this process. S100B is one of the numerous pro-inflammatory molecules produced by astrocytes, which is up regulated in AD and is found associated with plaques [1].
S100B is a small dimeric protein whose structure and functional regulatory interactions with other proteins, including the multi-ligand receptor RAGE. S100B has a broad range of cellular concentrations (from nano to micromolar) that explains why S100B is found as functional tetramers, hexamers and octamers, which enhance RAGE functional activation [2]. Many of the S100B mediated interactions are modulated by calcium-binding through EF hand motifs and by zinc- and copper-binding, to a site located at the dimer interface. These facts and our recent observation that S100 proteins have intrinsic ß-aggregation propensity [3] have prompted us to investigate S100B self-assembly reactions and co-aggregation phenomena involving other abundant neuronal proteins implicated in AD pathology, such as the amyloid ß peptide.
Along these lines, it became critical to develop tools to modulate the formation of S100B assemblies; among such reagents are nanobodies, which are conformation sensitive antibodies. In addition, these high-affinity single-domain antibodies derived from the atypical immunoglobulins from Camelidae have a small size (~15 kDa) and can be expressed in bacterial expression systems. Through Instruct, we have successfully accessed the Nanobodies4Instruct nanobody production facility with the goal to develop these molecules against S100B oligomers. These tools will be critical to establish future structural mechanistic studies and cellular assays that will uncover new roles of S100B oligomers in brain processes and AD neurodegeneration.
Accessibility: Document exists in file
Language:
eng
Author:
Cristóvão, J. S.
Secondary author(s):
Gomes, C. M.
Document type:
Online abstract
Reference:
Cristóvão, J. S., & Gomes, C. M. (2016). Developing nanobodies to manipulate protein:protein interaction in neurodegenerative diseases. aper presented ath the PCISBIO Day, Oeiras, Portugal. Abstract retrieved at http://www.itqb.unl.pt/meetings-and-courses/pcisbio/program-1/abstractsjcristovao.pdf
Indexed document: No

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Novo ficheiro

DocumentS100 proteins as novel modifiers of proteostasis in health and disease. in 2nd non-globular proteins in molecular physiopathology2016

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2014
Location: BF-GMS
Title:
2014 Grants
Start date: 2015-01

Reference code: PT/FB/BL-2014-343
Location: BF-GMS
Title:
343 - Proteotoxic insults and synaptic dysfunction in the aging brain
Duration: 2015-06 - 2019-01
Researcher(s):
Cláudio Emanuel Moreira Gomes, Andreas Martin Grabrucker, Joana Margarida Lopes da Silva Cristóvão, Sónia Cristina Alves Dickson Leal Solano
Institution(s): FCiências.ID – Associação para a Investigação e Desenvolvimento de Ciências (Portugal); Neurocenter of Ulm University (Germany)
Contents: Contents:
Application form
Correspondence
Progress report
Final report
Articles
Author: Gomes, C.
Secondary author(s):
Grabrucker, A., Cristóvão, J., Solano, S.
Keywords:
Protein homeostasis / Brain biometals / Neuroinflammation / Synaptic Biochemistry / Psychophysiology

Reference code: PT/FB/BL-2014-343.10
Location: BF-GMS
Title:
S100 proteins as novel modifiers of proteostasis in health and disease. in 2nd non-globular proteins in molecular physiopathology
Publication year: 2016
URL:
https://www.vin.bg.ac.rs/180/cost_bm1405/docs/Book_of_Abstracts.pdf
Abstract/Results: ABSTRACT:
S100 proteins are vertebrate-specific signaling molecules which have a dynamic cellular range of concentrations and oligomeric states, and are involved in diverse cellular processes. Structurally they are typically homodimers, containing two EF-hand type Ca2+ binding sites and, in some cases, additionally regulatory Zn2+ and Cu2+ binding sites [1]. S100 proteins are involved in aspects of regulation of proliferation, differentiation, apoptosis, Ca2+ homeostasis, energy metabolism, inflammation and migration/invasion through interactions with a variety of target proteins including enzymes, cytoskeletal subunits, receptors, transcription factors an nucleic acids. Many S100 proteins exert extracellular regulatory effects and expression of a particular S100 protein can be induced upon pathological circumstances in a cell type that does not express it in normal physiological conditions. Thus, extracellular S100 proteins exert regulatory activities over a vast number of cells and are engaged in multiple cellular processes such as innate and adaptive immune responses, cell migration and chemotaxis, tissue development and repair, tumor cell invasion and neuroinflammation [2].
Age-related neurodegenerative diseases, such as Alzheimer’s disease (AD), are associated with loss of neurons structure or function and a decay in brain and cognitive functions. Nowadays, there are approximately 50 neurodisorders, in which dysregulated protein expression is a common feature, correlate with the misfolding of normally soluble proteins and their subsequent conversion into aggregates [3]. Previous work from our laboratory suggests that S100s influence proteostasis across these disease-states. One such finding relates to the observation that S100 proteins are aggregation prone proteins that form amyloid oligomers and therefore will influence downstream signaling and overall cell proteostasis. Another important point is that S100 proteins forms amyloids structures in pro-inflammatory environments and that mechanism is facilitated by metal ions, like calcium, cooper or zinc [4]. Preliminary results suggest that the S100A8 and A9 regulation mechanisms occur through protein-protein interactions under mediation of metal ion binding, influencing their aggregation. Further, it is also known that S100A8 diffuse aggregates precede the formation of plaques in AD mice models [5]. Yet, the specific mechanism and global processes through which S100 aggregation occurs and the manner in which it can induce pathogenic behavior remain unclear.
In this project, we will undertake a systems approach combining molecular and cellular studies in neurodegeneration models, interactome and proteomics analysis, chemical biology peptidomics and bioimaging to uncover the mechanisms underlying alterations in protein homeostasis networks, resulting from the altered S100 functions. With this approach we seek to explore new roles of S100 proteins as novel modifiers of proteostasis networks in disease.
Accessibility: Document exists in file
Language:
eng
Author:
Romão, M.
Secondary author(s):
Gomes, C.
Document type:
Conference abstract
Reference:
Romão, M. A. (2016). S100 proteins as novel modifiers of proteostasis in health and disease. in 2nd non-globular proteins in molecular physiopathology. In Abstract Book of the 2nd Symposum Non-globular proteins in molecular physiopathology, Belgrade, September 15-17.
Indexed document: No

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