Human Albumin Impairs Amyloid β-peptide Fibrillation Through its C-terminus: From docking Modeling to Protection Against Neurotoxicity in Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative process characterized by the accumulation of extracellular deposits of amyloid β-peptide (Aβ), which induces neuronal death. Monomeric Aβ is not toxic but tends to aggregate into β-sheets that are neurotoxic. Therefore to prevent or delay AD onset...

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Autores: Picón Pagès, Pol, Bonet, Jaume, García García, Javier, Garcia Buendia, Joan, Gutierrez, Daniela, Valle, Javier, Gómez Casuso, Carmen E.S., Sidelkivska, Valeriya, Álvarez, Alejandra, Perálvarez Marín, Alex, Suades, Albert, Fernàndez Busquets, Xavier, Andreu, David, Vicente García, Rubén, 1978-, Oliva Miguel, Baldomero, Muñoz, Francisco J.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/139546
Acceso en línea:https://hdl.handle.net/2445/139546
Access Level:acceso abierto
Palabra clave:Malaltia d'Alzheimer
Albúmines
Alzheimer's disease
Albumins
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spelling Human Albumin Impairs Amyloid β-peptide Fibrillation Through its C-terminus: From docking Modeling to Protection Against Neurotoxicity in Alzheimer's diseasePicón Pagès, PolBonet, JaumeGarcía García, JavierGarcia Buendia, JoanGutierrez, DanielaValle, JavierGómez Casuso, Carmen E.S.Sidelkivska, ValeriyaÁlvarez, AlejandraPerálvarez Marín, AlexSuades, AlbertFernàndez Busquets, XavierAndreu, DavidVicente García, Rubén, 1978-Oliva Miguel, BaldomeroMuñoz, Francisco J.Malaltia d'AlzheimerAlbúminesAlzheimer's diseaseAlbuminsAlzheimer's disease (AD) is a neurodegenerative process characterized by the accumulation of extracellular deposits of amyloid β-peptide (Aβ), which induces neuronal death. Monomeric Aβ is not toxic but tends to aggregate into β-sheets that are neurotoxic. Therefore to prevent or delay AD onset and progression one of the main therapeutic approaches would be to impair Aβ assembly into oligomers and fibrils and to promote disaggregation of the preformed aggregate. Albumin is the most abundant protein in the cerebrospinal fluid and it was reported to bind Aβ impeding its aggregation. In a previous work we identified a 35-residue sequence of clusterin, a well-known protein that binds Aβ, that is highly similar to the C-terminus (CTerm) of albumin. In this work, the docking experiments show that the average binding free energy of the CTerm-Aβ1–42 simulations was significantly lower than that of the clusterin-Aβ1–42 binding, highlighting the possibility that the CTerm retains albumin's binding properties. To validate this observation, we performed in vitro structural analysis of soluble and aggregated 1 μM Aβ1–42 incubated with 5 μM CTerm, equimolar to the albumin concentration in the CSF. Reversed-phase chromatography and electron microscopy analysis demonstrated a reduction of Aβ1–42 aggregates when the CTerm was present. Furthermore, we treated a human neuroblastoma cell line with soluble and aggregated Aβ1–42 incubated with CTerm obtaining a significant protection against Aβ-induced neurotoxicity. These in silico and in vitro data suggest that the albumin CTerm is able to impair Aβ aggregation and to promote disassemble of Aβ aggregates protecting neurons.Elsevier2019201920192019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion9 p.application/pdfhttps://hdl.handle.net/2445/139546Articles publicats en revistes (ISGlobal)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: http://dx.doi.org/10.1016/j.csbj.2019.06.017Computational and Structural Biotechnology Journal, 2019, vol. 17, p. 963-971http://dx.doi.org/10.1016/j.csbj.2019.06.017cc by-nc-nd (c) Elsevier, 2019http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1395462026-05-29T05:05:01Z
dc.title.none.fl_str_mv Human Albumin Impairs Amyloid β-peptide Fibrillation Through its C-terminus: From docking Modeling to Protection Against Neurotoxicity in Alzheimer's disease
title Human Albumin Impairs Amyloid β-peptide Fibrillation Through its C-terminus: From docking Modeling to Protection Against Neurotoxicity in Alzheimer's disease
spellingShingle Human Albumin Impairs Amyloid β-peptide Fibrillation Through its C-terminus: From docking Modeling to Protection Against Neurotoxicity in Alzheimer's disease
Picón Pagès, Pol
Malaltia d'Alzheimer
Albúmines
Alzheimer's disease
Albumins
title_short Human Albumin Impairs Amyloid β-peptide Fibrillation Through its C-terminus: From docking Modeling to Protection Against Neurotoxicity in Alzheimer's disease
title_full Human Albumin Impairs Amyloid β-peptide Fibrillation Through its C-terminus: From docking Modeling to Protection Against Neurotoxicity in Alzheimer's disease
title_fullStr Human Albumin Impairs Amyloid β-peptide Fibrillation Through its C-terminus: From docking Modeling to Protection Against Neurotoxicity in Alzheimer's disease
title_full_unstemmed Human Albumin Impairs Amyloid β-peptide Fibrillation Through its C-terminus: From docking Modeling to Protection Against Neurotoxicity in Alzheimer's disease
title_sort Human Albumin Impairs Amyloid β-peptide Fibrillation Through its C-terminus: From docking Modeling to Protection Against Neurotoxicity in Alzheimer's disease
dc.creator.none.fl_str_mv Picón Pagès, Pol
Bonet, Jaume
García García, Javier
Garcia Buendia, Joan
Gutierrez, Daniela
Valle, Javier
Gómez Casuso, Carmen E.S.
Sidelkivska, Valeriya
Álvarez, Alejandra
Perálvarez Marín, Alex
Suades, Albert
Fernàndez Busquets, Xavier
Andreu, David
Vicente García, Rubén, 1978-
Oliva Miguel, Baldomero
Muñoz, Francisco J.
author Picón Pagès, Pol
author_facet Picón Pagès, Pol
Bonet, Jaume
García García, Javier
Garcia Buendia, Joan
Gutierrez, Daniela
Valle, Javier
Gómez Casuso, Carmen E.S.
Sidelkivska, Valeriya
Álvarez, Alejandra
Perálvarez Marín, Alex
Suades, Albert
Fernàndez Busquets, Xavier
Andreu, David
Vicente García, Rubén, 1978-
Oliva Miguel, Baldomero
Muñoz, Francisco J.
author_role author
author2 Bonet, Jaume
García García, Javier
Garcia Buendia, Joan
Gutierrez, Daniela
Valle, Javier
Gómez Casuso, Carmen E.S.
Sidelkivska, Valeriya
Álvarez, Alejandra
Perálvarez Marín, Alex
Suades, Albert
Fernàndez Busquets, Xavier
Andreu, David
Vicente García, Rubén, 1978-
Oliva Miguel, Baldomero
Muñoz, Francisco J.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malaltia d'Alzheimer
Albúmines
Alzheimer's disease
Albumins
topic Malaltia d'Alzheimer
Albúmines
Alzheimer's disease
Albumins
description Alzheimer's disease (AD) is a neurodegenerative process characterized by the accumulation of extracellular deposits of amyloid β-peptide (Aβ), which induces neuronal death. Monomeric Aβ is not toxic but tends to aggregate into β-sheets that are neurotoxic. Therefore to prevent or delay AD onset and progression one of the main therapeutic approaches would be to impair Aβ assembly into oligomers and fibrils and to promote disaggregation of the preformed aggregate. Albumin is the most abundant protein in the cerebrospinal fluid and it was reported to bind Aβ impeding its aggregation. In a previous work we identified a 35-residue sequence of clusterin, a well-known protein that binds Aβ, that is highly similar to the C-terminus (CTerm) of albumin. In this work, the docking experiments show that the average binding free energy of the CTerm-Aβ1–42 simulations was significantly lower than that of the clusterin-Aβ1–42 binding, highlighting the possibility that the CTerm retains albumin's binding properties. To validate this observation, we performed in vitro structural analysis of soluble and aggregated 1 μM Aβ1–42 incubated with 5 μM CTerm, equimolar to the albumin concentration in the CSF. Reversed-phase chromatography and electron microscopy analysis demonstrated a reduction of Aβ1–42 aggregates when the CTerm was present. Furthermore, we treated a human neuroblastoma cell line with soluble and aggregated Aβ1–42 incubated with CTerm obtaining a significant protection against Aβ-induced neurotoxicity. These in silico and in vitro data suggest that the albumin CTerm is able to impair Aβ aggregation and to promote disassemble of Aβ aggregates protecting neurons.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/139546
url https://hdl.handle.net/2445/139546
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/10.1016/j.csbj.2019.06.017
Computational and Structural Biotechnology Journal, 2019, vol. 17, p. 963-971
http://dx.doi.org/10.1016/j.csbj.2019.06.017
dc.rights.none.fl_str_mv cc by-nc-nd (c) Elsevier, 2019
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Elsevier, 2019
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9 p.
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (ISGlobal)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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