{"entity": "publication", "iuid": "ce0177b7c42141d582b314bf3611f72a", "timestamp": "2026-07-15T22:56:43.389Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ce0177b7c42141d582b314bf3611f72a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ce0177b7c42141d582b314bf3611f72a"}}, "title": "Regulation of \u03b1-synuclein by chaperones in mammalian cells.", "authors": [{"family": "Burmann", "given": "Bj\u00f6rn M", "initials": "BM"}, {"family": "Gerez", "given": "Juan A", "initials": "JA"}, {"family": "Mate\u010dko-Burmann", "given": "Irena", "initials": "I"}, {"family": "Campioni", "given": "Silvia", "initials": "S"}, {"family": "Kumari", "given": "Pratibha", "initials": "P"}, {"family": "Ghosh", "given": "Dhiman", "initials": "D"}, {"family": "Mazur", "given": "Adam", "initials": "A"}, {"family": "Aspholm", "given": "Emelie E", "initials": "EE"}, {"family": "\u0160ulskis", "given": "Darius", "initials": "D"}, {"family": "Wawrzyniuk", "given": "Magdalena", "initials": "M"}, {"family": "Bock", "given": "Thomas", "initials": "T"}, {"family": "Schmidt", "given": "Alexander", "initials": "A"}, {"family": "R\u00fcdiger", "given": "Stefan G D", "initials": "SGD"}, {"family": "Riek", "given": "Roland", "initials": "R"}, {"family": "Hiller", "given": "Sebastian", "initials": "S"}], "type": "journal article", "published": "2020-01-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "577", "issue": "7788", "pages": "127-132", "issn-l": "0028-0836"}, "abstract": "Neurodegeneration in patients with Parkinson's disease is correlated with the occurrence of Lewy bodies-intracellular inclusions that contain aggregates of the intrinsically disordered protein \u03b1-synuclein1. The aggregation propensity of \u03b1-synuclein in cells is modulated by specific factors that include post-translational modifications2,3, Abelson-kinase-mediated phosphorylation4,5 and interactions with intracellular machineries such as molecular chaperones, although the underlying mechanisms are unclear6-8. Here we systematically characterize the interaction of molecular chaperones with \u03b1-synuclein in vitro as well as in cells at the atomic level. We find that six highly divergent molecular chaperones commonly recognize a canonical motif in \u03b1-synuclein, consisting of the N terminus and a segment around Tyr39, and hinder the aggregation of \u03b1-synuclein. NMR experiments9 in cells show that the same transient interaction pattern is preserved inside living mammalian cells. Specific inhibition of the interactions between \u03b1-synuclein and the chaperone HSC70 and members of the HSP90 family, including HSP90\u03b2, results in transient membrane binding and triggers a remarkable re-localization of \u03b1-synuclein to the mitochondria and concomitant formation of aggregates. Phosphorylation of \u03b1-synuclein at Tyr39 directly impairs the interaction of \u03b1-synuclein with chaperones, thus providing a functional explanation for the role of Abelson kinase in Parkinson's disease. Our results establish a master regulatory mechanism of \u03b1-synuclein function and aggregation in mammalian cells, extending the functional repertoire of molecular chaperones and highlighting new perspectives for therapeutic interventions for Parkinson's disease.", "doi": "10.1038/s41586-019-1808-9", "pmid": "31802003", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41586-019-1808-9"}, {"db": "pmc", "key": "PMC6930850"}, {"db": "mid", "key": "EMS84680"}], "notes": [], "created": "2020-01-07T11:00:49.664Z", "modified": "2025-10-17T13:03:57.242Z"}