Tridimensional Structural Analysis of Tau Isoforms Generated by Intronic Retention

Background: Tauopathies are a subset of neurodegenerative diseases characterized by abnormal tau inclusions. Recently, we have discovered a new, human specific, tau isoform termed W-tau that originates by intron 12 retention. Our preliminary data suggests this newly discovered W-tau isoform might pr...

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Detalles Bibliográficos
Autores: Domene Serrano, Indalo, Cuadros, Raquel, Hernández Pérez, Félix, Ávila, Jesús, Santa-María, Ismael
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/716161
Acceso en línea:http://hdl.handle.net/10486/716161
https://dx.doi.org/10.3233/ADR-230074
Access Level:acceso abierto
Palabra clave:Alzheimer’s disease
deep learning
intron retention
isoform
polymerization
splicing
tau protein
tridimensional structure
Biología y Biomedicina / Biología
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spelling Tridimensional Structural Analysis of Tau Isoforms Generated by Intronic RetentionDomene Serrano, IndaloCuadros, RaquelHernández Pérez, FélixÁvila, JesúsSanta-María, IsmaelAlzheimer’s diseasedeep learningintron retentionisoformpolymerizationsplicingtau proteintridimensional structureBiología y Biomedicina / BiologíaBackground: Tauopathies are a subset of neurodegenerative diseases characterized by abnormal tau inclusions. Recently, we have discovered a new, human specific, tau isoform termed W-tau that originates by intron 12 retention. Our preliminary data suggests this newly discovered W-tau isoform might prevent aberrant aggregation of other tau isoforms but is significantly downregulated in tauopathies such as Alzheimer´s disease. Objective: To accurately predict, examine, and understand tau protein structure and the conformational basis for the neuroprotective role of W-tau. Methods: A tridimensional deep learning-based approach and in vitro polymerization assay was included to accurately predict, analyze, and understand tau protein structure and the conformational basis for the neuroprotective role of W-tau. Results: Our findings demonstrate: a) the predicted protein tridimensionality structure of the tau isoforms raised by intron retention and their comparison with the other tau isoforms; b) the interaction of W-tau peptide (from W-tau isoform) with other tau isoforms; c) the effect of W-tau peptide in the polymerization of those tau isoforms. Conclusions: This study supports the importance of the structure-function relationship on the neuroprotective behavior of W-tau inhibiting tau fibrillization in vitroThis work has been supported by grants from the Spanish Ministry of Science: PID2020-113204GB-I00 (F.H.) and PID2021-123859OB-100 from MCIN/AEI/10.13039/501100011033 / FEDER, UE (J.A.). The Centro de Biología Molecular Severo Ochoa (CBMSO) is a Severo Ochoa Center of Excellence (MICIN, award CEX2021-001154-S)IOS Press BVDepartamento de Biología MolecularFacultad de Ciencias20232023-11-22research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/716161https://dx.doi.org/10.3233/ADR-230074reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7161612026-06-23T12:46:27Z
dc.title.none.fl_str_mv Tridimensional Structural Analysis of Tau Isoforms Generated by Intronic Retention
title Tridimensional Structural Analysis of Tau Isoforms Generated by Intronic Retention
spellingShingle Tridimensional Structural Analysis of Tau Isoforms Generated by Intronic Retention
Domene Serrano, Indalo
Alzheimer’s disease
deep learning
intron retention
isoform
polymerization
splicing
tau protein
tridimensional structure
Biología y Biomedicina / Biología
title_short Tridimensional Structural Analysis of Tau Isoforms Generated by Intronic Retention
title_full Tridimensional Structural Analysis of Tau Isoforms Generated by Intronic Retention
title_fullStr Tridimensional Structural Analysis of Tau Isoforms Generated by Intronic Retention
title_full_unstemmed Tridimensional Structural Analysis of Tau Isoforms Generated by Intronic Retention
title_sort Tridimensional Structural Analysis of Tau Isoforms Generated by Intronic Retention
dc.creator.none.fl_str_mv Domene Serrano, Indalo
Cuadros, Raquel
Hernández Pérez, Félix
Ávila, Jesús
Santa-María, Ismael
author Domene Serrano, Indalo
author_facet Domene Serrano, Indalo
Cuadros, Raquel
Hernández Pérez, Félix
Ávila, Jesús
Santa-María, Ismael
author_role author
author2 Cuadros, Raquel
Hernández Pérez, Félix
Ávila, Jesús
Santa-María, Ismael
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv Alzheimer’s disease
deep learning
intron retention
isoform
polymerization
splicing
tau protein
tridimensional structure
Biología y Biomedicina / Biología
topic Alzheimer’s disease
deep learning
intron retention
isoform
polymerization
splicing
tau protein
tridimensional structure
Biología y Biomedicina / Biología
description Background: Tauopathies are a subset of neurodegenerative diseases characterized by abnormal tau inclusions. Recently, we have discovered a new, human specific, tau isoform termed W-tau that originates by intron 12 retention. Our preliminary data suggests this newly discovered W-tau isoform might prevent aberrant aggregation of other tau isoforms but is significantly downregulated in tauopathies such as Alzheimer´s disease. Objective: To accurately predict, examine, and understand tau protein structure and the conformational basis for the neuroprotective role of W-tau. Methods: A tridimensional deep learning-based approach and in vitro polymerization assay was included to accurately predict, analyze, and understand tau protein structure and the conformational basis for the neuroprotective role of W-tau. Results: Our findings demonstrate: a) the predicted protein tridimensionality structure of the tau isoforms raised by intron retention and their comparison with the other tau isoforms; b) the interaction of W-tau peptide (from W-tau isoform) with other tau isoforms; c) the effect of W-tau peptide in the polymerization of those tau isoforms. Conclusions: This study supports the importance of the structure-function relationship on the neuroprotective behavior of W-tau inhibiting tau fibrillization in vitro
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-11-22
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/716161
https://dx.doi.org/10.3233/ADR-230074
url http://hdl.handle.net/10486/716161
https://dx.doi.org/10.3233/ADR-230074
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv IOS Press BV
publisher.none.fl_str_mv IOS Press BV
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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