α-Synuclein Drives Tau's Cytotoxic Aggregates Formation through Hydrophobic Interactions

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dc.article.numbere202300257
dc.contributor.authorOjeda, Ana
dc.contributor.authorCofré, Valentina
dc.contributor.authorMelo, Francisco
dc.contributor.authorCaballero, Leonardo
dc.contributor.authorFuentealba Patino, Denis Alberto
dc.contributor.authorCornejo, Alberto
dc.date.accessioned2024-04-15T08:00:28Z
dc.date.available2024-04-15T08:00:28Z
dc.date.issued2023
dc.description.abstractTau and α-synuclein are proteins involved in pathologies known as tauopathies and synucleinopathies, respectively. Moreover, evidence shows that there is a crosstalk between them as is seen in the brains of individuals with sporadic neurodegenerative disorders. Based on that, we present data showing that the hydrophobic α-peptide 71VTGVTAVAQKTV82 induces the aggregation of the full-length tau fragment in the absence of heparin assessed by ThT. Moreover, AFM images reveal the presence of straight filaments and amorphous aggregates of full-length tau in the presence of the α-peptide. Additionally, ITC experiments showed the interaction of the α-peptide with tau full-length (441 amino acids),4R (amino acids from 244 to 369), and both hexapeptides 275VQIINK280 and 306VQIVYK311 through hydrophobic interactions. The Raman spectroscopy spectra showed conformational changes in the Amide region in the aggregates formed with full-length tau and α-syn peptide. Furthermore, the incubation of extracellular aggregates with N2a cells showed morphological differences in the cellular body and the nucleus suggesting cell death. Moreover,, the incubation of different types of aggregates in cell culture provokes the release of Lactate dehydrogenase (LDH). Altogether, we found that α-synuclein peptide can drive the aggregation of full-length tau-provoking morphological and structural changes evoking cytotoxic effects.
dc.description.funderCentre for Social Conflict and Cohesion Studies (COES)
dc.description.funderAlberto Hurtado University
dc.description.funderFONDECYT
dc.description.funderANID
dc.format.extent458 páginas
dc.fuente.origenScopus
dc.identifier.doidoi.org/10.1002/cplu.202300257
dc.identifier.eissn1467-8659
dc.identifier.isbn978-1-119-52131-0
dc.identifier.issn21926506
dc.identifier.pubmedidMEDLINE:34444039
dc.identifier.scopusidSCOPUS_ID:85173068015
dc.identifier.urihttps://doi.org/doi.org/10.1002/cplu.202300257
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/85088
dc.identifier.wosidWOS:001013034400001
dc.information.autorucEscuela de Química; Fuentealba Patino, Denis Alberto; 0000-0003-4798-7204; 160255
dc.issue.numero10
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final17
dc.pagina.inicio1
dc.publisherWiley
dc.relation.ispartofCiudad y Territorio Estudios Territoriales
dc.revistaChemPlusChem
dc.rightsacceso restringido
dc.subjectCell death
dc.subjectConformational changes
dc.subjectHydrophobic interactions
dc.subjectTau
dc.subjectα-syn
dc.subject.ddc572.65
dc.subject.deweyBiologíaes_ES
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleα-Synuclein Drives Tau's Cytotoxic Aggregates Formation through Hydrophobic Interactions
dc.typeartículo
dc.volumen88
sipa.codpersvinculados160255
sipa.indexScopus
sipa.trazabilidadCarga WOS-SCOPUS;15-04-2024
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