{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nuber S"],"funding":["Harvard NeuroDiscovery Center","NINDS NIH HHS","NIH"],"pagination":["75-90.e5"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6211795"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["100(1)"],"pubmed_abstract":["α-Synuclein (αS) regulates vesicle exocytosis but forms insoluble deposits in Parkinson's disease (PD). Developing disease-modifying therapies requires animal models that reproduce cardinal features of PD. We recently described a previously unrecognized physiological form of αS, α-helical tetramers, and showed that familial PD-causing missense mutations shift tetramers to aggregation-prone monomers. Here, we generated mice expressing the fPD E46K mutation plus 2 homologous E→K mutations in adjacent KTKEGV motifs. This tetramer-abrogating mutant causes phenotypes similar to PD. αS monomers accumulate at membranes and form vesicle-rich inclusions. αS becomes insoluble, proteinase K-resistant, Ser129-phosphorylated, and C-terminally truncated, as in PD. These changes affect regions controllin"],"journal":["Neuron"],"pubmed_title":["Abrogating Native α-Synuclein Tetramers in Mice Causes a L-DOPA-Responsive Motor Syndrome Closely Resembling Parkinson's Disease."],"pmcid":["PMC6211795"],"funding_grant_id":["RF1 NS083845","NS083845","R01 NS099328","NS103123","R21 NS103123","R01 NS083845","NS 099328","R01 NS109510"],"pubmed_authors":["Rajsombath M","Winkler J","Muller CP","Caldarone B","Dettmer U","Selkoe DJ","Nuber S","Ericsson M","Minakaki G"],"additional_accession":[]},"is_claimable":false,"name":"Abrogating Native α-Synuclein Tetramers in Mice Causes a L-DOPA-Responsive Motor Syndrome Closely Resembling Parkinson's Disease.","description":"α-Synuclein (αS) regulates vesicle exocytosis but forms insoluble deposits in Parkinson's disease (PD). Developing disease-modifying therapies requires animal models that reproduce cardinal features of PD. We recently described a previously unrecognized physiological form of αS, α-helical tetramers, and showed that familial PD-causing missense mutations shift tetramers to aggregation-prone monomers. Here, we generated mice expressing the fPD E46K mutation plus 2 homologous E→K mutations in adjacent KTKEGV motifs. This tetramer-abrogating mutant causes phenotypes similar to PD. αS monomers accumulate at membranes and form vesicle-rich inclusions. αS becomes insoluble, proteinase K-resistant, Ser129-phosphorylated, and C-terminally truncated, as in PD. These changes affect regions controllin","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Oct","modification":"2025-04-04T21:37:31.984Z","creation":"2019-10-16T07:01:05Z"},"accession":"S-EPMC6211795","cross_references":{"pubmed":["30308173"],"doi":["10.1016/j.neuron.2018.09.014"]}}