{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rozales K"],"funding":["European Research Council"],"pagination":["516"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8792056"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(1)"],"pubmed_abstract":["Protein aggregation is a hallmark of neurodegeneration. Here, we find that Huntington's disease-related HTT-polyQ aggregation induces a cellular proteotoxic stress response, while ALS-related mutant FUS (mutFUS) aggregation leads to deteriorated proteostasis. Further exploring chaperone function as potential modifiers of pathological aggregation in these contexts, we reveal divergent effects of naturally-occurring chaperone isoforms on different aggregate types. We identify a complex of the full-length (FL) DNAJB14 and DNAJB12, that substantially protects from mutFUS aggregation, in an HSP70-dependent manner. Their naturally-occurring short isoforms, however, do not form a complex, and lose their ability to preclude mutFUS aggregation. In contrast, DNAJB12-short alleviates, while DNAJB12-F"],"journal":["Nature communications"],"pubmed_title":["Differential roles for DNAJ isoforms in HTT-polyQ and FUS aggregation modulation revealed by chaperone screens."],"pmcid":["PMC8792056"],"funding_grant_id":["677776","851919"],"pubmed_authors":["Goldman H","Shalgi R","Saida N","Younis A","Meller A","Berlin S","Rozales K","Kellerman L","Heinrich R"],"additional_accession":[]},"is_claimable":false,"name":"Differential roles for DNAJ isoforms in HTT-polyQ and FUS aggregation modulation revealed by chaperone screens.","description":"Protein aggregation is a hallmark of neurodegeneration. Here, we find that Huntington's disease-related HTT-polyQ aggregation induces a cellular proteotoxic stress response, while ALS-related mutant FUS (mutFUS) aggregation leads to deteriorated proteostasis. Further exploring chaperone function as potential modifiers of pathological aggregation in these contexts, we reveal divergent effects of naturally-occurring chaperone isoforms on different aggregate types. We identify a complex of the full-length (FL) DNAJB14 and DNAJB12, that substantially protects from mutFUS aggregation, in an HSP70-dependent manner. Their naturally-occurring short isoforms, however, do not form a complex, and lose their ability to preclude mutFUS aggregation. In contrast, DNAJB12-short alleviates, while DNAJB12-F","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jan","modification":"2026-05-31T01:15:55.778Z","creation":"2024-11-09T08:01:10.949Z"},"accession":"S-EPMC8792056","cross_references":{"pubmed":["35082301"],"doi":["10.1038/s41467-022-27982-w"]}}