{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T04:08:33Z","timestamp":1773893313488,"version":"3.50.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"MJ Fox Foundation"},{"name":"Cure PD Trust"},{"name":"Parkinson\u2019s UK"},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UK Dementia ResearchInstitute"},{"DOI":"10.13039\/501100017510","name":"UK DRI Ltd","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000320","name":"Alzheimer's Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000320","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alzheimer's Research UK"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\u03b1-Synuclein aggregation at the synapse is an early event in Parkinson\u2019s disease and is associated with impaired striatal synaptic function and dopaminergic neuronal death. The cysteine string protein (CSP\u03b1) and \u03b1-synuclein have partially overlapping roles in maintaining synaptic function and mutations in each cause neurodegenerative diseases. CSP\u03b1 is a member of the DNAJ\/HSP40 family of co-chaperones and like \u03b1-synuclein, chaperones the SNARE complex assembly and controls neurotransmitter release. \u03b1-Synuclein can rescue neurodegeneration in CSP\u03b1KO mice. However, whether \u03b1-synuclein aggregation alters CSP\u03b1 expression and function is unknown. Here we show that \u03b1-synuclein aggregation at the synapse is associated with a decrease in synaptic CSP\u03b1 and a reduction in the complexes that CSP\u03b1 forms with HSC70 and STGa. We further show that viral delivery of CSP\u03b1 rescues in vitro the impaired vesicle recycling in PC12 cells with \u03b1-synuclein aggregates and in vivo reduces synaptic \u03b1-synuclein aggregates increasing monomeric \u03b1-synuclein and restoring normal dopamine release in 1-120h\u03b1Syn mice. These novel findings reveal a mechanism by which \u03b1-synuclein aggregation alters CSP\u03b1 at the synapse, and show that CSP\u03b1 rescues \u03b1-synuclein aggregation-related phenotype in 1-120h\u03b1Syn mice similar to the effect of \u03b1-synuclein in CSP\u03b1KO mice. These results implicate CSP\u03b1 as a potential therapeutic target for the treatment of early-stage Parkinson\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awab076","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T07:15:23Z","timestamp":1615360523000},"page":"1661-1669","source":"Crossref","is-referenced-by-count":23,"title":["CSP\u03b1 reduces aggregates and rescues striatal dopamine release in \u03b1-synuclein transgenic mice"],"prefix":"10.1093","volume":"144","author":[{"given":"Laura","family":"Cal\u00f3","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge, UK"},{"name":"Dementia Research Institute, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4777-5239","authenticated-orcid":false,"given":"Eric","family":"Hidari","sequence":"additional","affiliation":[{"name":"Dementia Research Institute, University of Cambridge, Cambridge, UK"},{"name":"Department of Chemistry, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5082-9576","authenticated-orcid":false,"given":"Michal","family":"Wegrzynowicz","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge, UK"},{"name":"Laboratory of Molecular Basis of Neurodegeneration, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey W","family":"Dalley","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Cambridge, Cambridge, UK"},{"name":"Department of Psychiatry, Hershel Smith Building for Brain and Mind Sciences, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard L","family":"Schneider","sequence":"additional","affiliation":[{"name":"Brain Mind Institute, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), 1015 Lausanne, Switzerland"},{"name":"Bertarelli Platform for Gene Therapy, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), 1202 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8323-9492","authenticated-orcid":false,"given":"Martyna","family":"Podgajna","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Basis of Neurodegeneration, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleg","family":"Anichtchik","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Carlson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Dementia Research Institute, University of Cambridge, Cambridge, UK"},{"name":"Department of Chemistry, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Grazia","family":"Spillantini","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Clifford Allbutt Building, 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