{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jager S"],"funding":["Bundesministerium für Bildung und Forschung","Deutsche Forschungsgemeinschaft (DFG)","Agence Nationale de la Recherche (ANR)","Association France Parkinson","Agence Nationale de la Recherche","Alzheimer Forschung Initiative (AFI)","Lundbeck Foundation (Lundbeckfonden)","Association France Parkinson (France Parkinson)","Alzheimer Forschung Initiative","Bundesministerium für Bildung und Forschung (BMBF)","Lundbeck Foundation","Deutsche Forschungsgemeinschaft","Novo Nordisk Fonden (NNF)","Dutch Research Council (NWO)","NWO | Exacte en Natuurwetenschappen (ENW)","Novo Nordisk Fonden","NWO | Exacte en Natuurwetenschappen"],"pagination":["6499-6526"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12623964"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(22)"],"pubmed_abstract":["Pathological aggregation of α-synuclein into amyloid fibrils is a hallmark of synucleinopathies, including Parkinson's disease. Despite this commonality, synucleinopathies display divergent disease phenotypes that have been attributed to disease-specific three-dimensional structures of α-synuclein fibrils, each with unique toxic gain-of-function profiles. The Hsc70 chaperone is remarkable in its ability to disassemble pre-existing amyloid fibrils of different proteins in an ATP and co-chaperone-dependent manner. We find, however, using six well-defined conformational polymorphs of α-synuclein fibrils, that the activity of the Hsc70 disaggregase machinery is sensitive to differences in the amyloid conformation, confirming that fibril polymorphism directly affects interactions with the prote"],"journal":["The EMBO journal"],"pubmed_title":["Structural polymorphism of α-synuclein fibrils alters the pathway of Hsc70-mediated disaggregation."],"pmcid":["PMC12623964"],"funding_grant_id":["01ED1807A","17054","VI.Vidi.223.172","01ED1807B","217681","504257241","NNFSA170028392","ANR-22-PERM-0006","ANR-17-JPCD-0005-01","R366-2021-169"],"pubmed_authors":["Redeker V","Tittelmeier J","Wentink AS","Bellande T","Dang TL","Melki R","Nussbaum-Krammer C","Buell AK","Hennig J","Bukau B","Jager S"],"additional_accession":[]},"is_claimable":false,"name":"Structural polymorphism of α-synuclein fibrils alters the pathway of Hsc70-mediated disaggregation.","description":"Pathological aggregation of α-synuclein into amyloid fibrils is a hallmark of synucleinopathies, including Parkinson's disease. Despite this commonality, synucleinopathies display divergent disease phenotypes that have been attributed to disease-specific three-dimensional structures of α-synuclein fibrils, each with unique toxic gain-of-function profiles. The Hsc70 chaperone is remarkable in its ability to disassemble pre-existing amyloid fibrils of different proteins in an ATP and co-chaperone-dependent manner. We find, however, using six well-defined conformational polymorphs of α-synuclein fibrils, that the activity of the Hsc70 disaggregase machinery is sensitive to differences in the amyloid conformation, confirming that fibril polymorphism directly affects interactions with the prote","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-07-15T06:09:29.883Z","creation":"2026-06-30T03:22:06.919Z"},"accession":"S-EPMC12623964","cross_references":{"pubmed":["41053261"],"doi":["10.1038/s44318-025-00573-3"]}}