ubiquitinylation of α-synuclein by carboxyl terminus hsp70-interacting protein (chip) is regulated by bcl-2-associated athanogene 5 (bag5)ubiquitinylationα-synuclein的羧基末端hsp70-interacting蛋白质(芯片)是由bcl-2-associated athanogene 5(bag5).pdfVIP

Ubiquitinylation of a-Synuclein by Carboxyl Terminus Hsp70-Interacting Protein (CHIP) Is Regulated by Bcl-2- Associated Athanogene 5 (BAG5) 1,2,4 . 1,3,4. 4 3,4 1 Lorraine V. Kalia * , Suneil K. Kalia , Hien Chau , Andres M. Lozano , Bradley T. Hyman , Pamela J. McLean1 1 Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, United States of America, 2 Division of Neurology, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Canada, 3 Division of Neurosurgery, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Canada, 4 Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Canada Abstract Parkinson’s disease (PD) is a common neurodegenerative condition in which abnormalities in protein homeostasis, or proteostasis, may lead to accumulation of the protein a-synuclein (a-syn). Mutations within or multiplications of the gene encoding a-syn are known to cause genetic forms of PD and polymorphisms in the gene are recently established risk factors for idiopathic PD. a-syn is a major component of Lewy bodies, the intracellular proteinaceous inclusions which are pathological hallmarks of most forms of PD. Recent evidence demonstrates that a-syn can self associate into soluble oligomeric species and implicates these a-syn oligomers in cell death. We have previously shown that carboxyl terminus of Hsp70-interacting protein (CHIP), a co-chaperone molecule with E3 ubiquitin li