Lysosomal Degradation of -synuclein in Vivo
نویسندگان
چکیده
Sally K. Mak, Alison L. McCormack, Amy B. Manning-Boğ, Ana Maria Cuervo and Donato A. Di Monte The Parkinson’s Institute, Sunnyvale, California 94085, Center for Health Sciences, SRI International, Menlo Park, California 94025 and Albert Einstein College of Medicine, Bronx, New York 10461 Running head: CMA and -synuclein in vivo Address correspondence to: Donato A. Di Monte: 333 Ravenswood Avenue, Menlo Park, CA 94025. Tel: (650) 859-2382; E-mail: [email protected]
منابع مشابه
The co-chaperone carboxyl terminus of Hsp70-interacting protein (CHIP) mediates alpha-synuclein degradation decisions between proteasomal and lysosomal pathways.
Alpha-synuclein is a major component of Lewy bodies, the pathological hallmark of Parkinson disease, dementia with Lewy bodies, and related disorders. Misfolding and aggregation of alpha-synuclein is thought to be a critical cofactor in the pathogenesis of certain neurodegenerative diseases. In the current study, we investigate the role of the carboxyl terminus of Hsp70-interacting protein (CHI...
متن کاملRegional Lysosomal Malfunction Underlies the Selectivity of α-Synuclein Neurodegeneration
Dysfunction of protein homoeostasis has been implicated in the pathogenesis of a diverse array of neurodegenerative disorders. However, each neurodegenerative disease is characterized by the accumulation of particular proteins in select regions of the brain. It remains unclear how dysfunction of a ubiquitous protein degradation pathway results in distinct pathologies. α-Synuclein is a protein w...
متن کاملUbiquitin ligase Nedd4 promotes alpha-synuclein degradation by the endosomal-lysosomal pathway.
α-Synuclein is an abundant brain protein that binds to lipid membranes and is involved in the recycling of presynaptic vesicles. In Parkinson disease, α-synuclein accumulates in intraneuronal inclusions often containing ubiquitin chains. Here we show that the ubiquitin ligase Nedd4, which functions in the endosomal-lysosomal pathway, robustly ubiquitinates α-synuclein, unlike ligases previously...
متن کاملEnhanced ubiquitin-dependent degradation by Nedd4 protects against α-synuclein accumulation and toxicity in animal models of Parkinson's disease
Parkinson's disease is a neurodegenerative disorder, characterized by accumulation and misfolding of α-synuclein. Although the level of α-synuclein in neurons is fundamentally linked to the onset of neurodegeneration, multiple pathways have been implicated in its degradation, and it remains unclear which are the critical ubiquitination enzymes that protect against α-synuclein accumulation in vi...
متن کاملDeficiency of ATP13A2 leads to lysosomal dysfunction, α-synuclein accumulation, and neurotoxicity.
The autophagy-lysosomal pathway plays an important role in the clearance of long-lived proteins and dysfunctional organelles. Lysosomal dysfunction has been implicated in several neurodegenerative disorders including Parkinson's disease and related synucleinopathies that are characterized by accumulations of α-synuclein in Lewy bodies. Recent identification of mutations in genes linked to lysos...
متن کامل