{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Brahmachari S"],"funding":["Diana Helis Henry Medical Research Foundation","Summer Student Fellowships","Johns Hopkins University School of Medicine and the Foundation’s Parkinson’s Disease Program M-1, M-2","NIH","JPB Foundation","Intramural Research Program","NINDS","Center for Cancer Research","Johns Hopkins Hospital","Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases","NCI","NINDS NIH HHS","Parkinson’s Disease Foundation","Morris K. Udall Parkinson’s Disease Research Center","American Parkinson Disease Association","Adrienne Helis Malvin Medical Research Foundation","NIGMS NIH HHS"],"pagination":["2380-2401"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6658849"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["142(8)"],"pubmed_abstract":["α-Synuclein misfolding and aggregation plays a major role in the pathogenesis of Parkinson's disease. Although loss of function mutations in the ubiquitin ligase, parkin, cause autosomal recessive Parkinson's disease, there is evidence that parkin is inactivated in sporadic Parkinson's disease. Whether parkin inactivation is a driver of neurodegeneration in sporadic Parkinson's disease or a mere spectator is unknown. Here we show that parkin in inactivated through c-Abelson kinase phosphorylation of parkin in three α-synuclein-induced models of neurodegeneration. This results in the accumulation of parkin interacting substrate protein (zinc finger protein 746) and aminoacyl tRNA synthetase complex interacting multifunctional protein 2 with increased parkin interacting substrate protein lev"],"journal":["Brain : a journal of neurology"],"pubmed_title":["Parkin interacting substrate zinc finger protein 746 is a pathological mediator in Parkinson's disease."],"pmcid":["PMC6658849"],"funding_grant_id":["T34 GM110517","R01 NS082205","NS082205","NS38377","T32 GM007753","H-2014","NS098006","P50 NS038377","H-2013","PDF-APDA-SFW-1650","R21 NS098006","PDF-SFW-1572"],"pubmed_authors":["Lee S","Kim D","Kim EJ","Shi R","Jiang H","Kumar M","Yun SP","Tessarollo L","Quintin S","Swing DA","Ge P","Dawson VL","Kim S","Dawson TM","Yuan C","Ko HS","Brahmachari S","Liu A","Mao X","Kam TI","Lee Y","Karuppagounder SS"],"additional_accession":[]},"is_claimable":false,"name":"Parkin interacting substrate zinc finger protein 746 is a pathological mediator in Parkinson's disease.","description":"α-Synuclein misfolding and aggregation plays a major role in the pathogenesis of Parkinson's disease. Although loss of function mutations in the ubiquitin ligase, parkin, cause autosomal recessive Parkinson's disease, there is evidence that parkin is inactivated in sporadic Parkinson's disease. Whether parkin inactivation is a driver of neurodegeneration in sporadic Parkinson's disease or a mere spectator is unknown. Here we show that parkin in inactivated through c-Abelson kinase phosphorylation of parkin in three α-synuclein-induced models of neurodegeneration. This results in the accumulation of parkin interacting substrate protein (zinc finger protein 746) and aminoacyl tRNA synthetase complex interacting multifunctional protein 2 with increased parkin interacting substrate protein lev","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Aug","modification":"2025-04-29T10:33:05.712Z","creation":"2025-04-06T19:30:21.653Z"},"accession":"S-EPMC6658849","cross_references":{"pubmed":["31237944"],"doi":["10.1093/brain/awz172"]}}