{"doi":"10.1021/acs.biochem.2c00581","title":"DJ-1 Molecular Chaperone Activity Depresses Tau Aggregation Propensity through Interaction with Monomers","abstract":"Tau aggregate-bearing lesions are pathological markers and potential mediators of tauopathic neurodegenerative diseases, including Alzheimer’s disease. The molecular chaperone DJ-1 colocalizes with tau pathology in these disorders, but it has been unclear what functional link exists between them. In this study, we examined the consequences of tau/DJ-1 interaction as isolated proteins in vitro . When added to full-length 2N4R tau under aggregation-promoting conditions, DJ-1 inhibited both the rate and extent of filament formation in a concentration-dependent manner. Inhibitory activity was low affinity, did not require ATP, and was not affected by substituting oxidation incompetent missense mutation C106A for wild-type DJ-1. In contrast, missense mutations previously linked to familial Parkinson’s disease and loss of α-synuclein chaperone activity, M26I and E64D, displayed diminished tau chaperone activity relative to wild-type DJ-1. Although DJ-1 directly bound the isolated microtubule-binding repeat region of tau protein, exposure of preformed tau seeds to DJ-1 did not diminish seeding activity in a biosensor cell model. These data reveal DJ-1 to be a holdase chaperone capable of engaging tau as a client in addition to α-synuclein. Our findings support a role for DJ-1 as part of an endogenous defense against the aggregation of these intrinsically disordered proteins.","journal":"Biochemistry","year":2023,"id":359068,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":728510,"name":"Carol J. Huseby","orcid":"0000-0002-9558-5560","position":1,"is_corresponding":false},{"id":1109724,"name":"Claire N. Hoffman","orcid":"0000-0002-6204-483X","position":2,"is_corresponding":false},{"id":317874,"name":"Steven Sher","orcid":"0000-0002-3788-3228","position":3,"is_corresponding":false},{"id":353219,"name":"Dalton T. Snyder","orcid":"0000-0003-2154-5002","position":4,"is_corresponding":false},{"id":1110160,"name":"Brayden Seal","orcid":null,"position":5,"is_corresponding":false},{"id":397430,"name":"Chunhua Yuan","orcid":"0000-0003-2209-4653","position":6,"is_corresponding":false},{"id":257824,"name":"Hongjun Fu","orcid":"0000-0001-5346-7075","position":7,"is_corresponding":false},{"id":242368,"name":"Vicki H. Wysocki","orcid":"0000-0003-0495-2538","position":8,"is_corresponding":false},{"id":890510,"name":"Flaviano Giorgini","orcid":"0000-0001-7881-9508","position":9,"is_corresponding":false},{"id":728511,"name":"Jeff Kuret","orcid":"0000-0002-8083-8406","position":10,"is_corresponding":false},{"id":1109723,"name":"Daniela Jimenez-Harrison","orcid":"0000-0003-0786-7988","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T01:13:52.889556Z","pmid":"36813261","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}