Proteolytic clearance of extracellular α-synuclein as a new therapeutic approach against Parkinson disease.
Many neurodegenerative diseases such as Alzheimer disease and Parkinson disease show similar characteristics. They typically show deposits of protein aggregates, the formation of which is considered important in their pathogenesis. Recently, aggregation-prone proteins have been shown to spread between cells and so may contribute to the pathogenesis of diseases like prion disease. Such a pathogenesis pathway is possibly common to many neurodegenerative diseases. If confirmed, it could allow the development of therapeutic interventions against many such diseases. In Parkinson disease, α-synuclein, a major component of cytosolic protein inclusions named Lewy body, has been shown to be released and taken up by cells, which may facilitate its progressive pathological spreading between cells. Accordingly, inhibition of spreading by targeting extracellular α-synuclein may represent a new therapy against Parkinson disease. Research into the intercellular spreading of extracellular protein aggregations of α-synuclein and its clearance pathway are reviewed here with a focus on the proteolytic clearance pathway as a therapeutic target for the treatment of Parkinson disease. Considering the similar characteristics of aggregation-prone proteins, these clearance systems might allow treatment of other neurodegenerative diseases beyond Parkinson disease.
['Park|Sang Myun|SM|', 'Kim|Kwang Soo|KS|']
D000818:Animals D016503:Drug Delivery Systems D005110:Extracellular Space D006801:Humans D010300:Parkinson Disease D011328:Prions D059748:Proteolysis D051844:alpha-Synuclein
α-synuclein Parkinson disease neurodegenerative disease aggregation-prone proteins prion matrix metalloproteinase neurosin plasmin protease proteolysis