Asparagine endopeptidase cleaves α-synuclein and mediates pathologic activities in Parkinson's disease.

ABSTRACT: Aggregated forms of α-synuclein play a crucial role in the pathogenesis of synucleinopathies such as Parkinson's disease (PD). However, the molecular mechanisms underlying the pathogenic effects of α-synuclein are not completely understood. Here we show that asparagine endopeptidase (AEP) cleaves human α-synuclein, triggers its aggregation and escalates its neurotoxicity, thus leading to dopaminergic neuronal loss and motor impairments in a mouse model. AEP is activated and cleaves human α-synuclein at N103 in an age-dependent manner. AEP is highly activated in human brains with PD, and it fragments α-synuclein, which is found aggregated in Lewy bodies. Overexpression of the AEP-cleaved α-synuclein_1-103 fragment in the substantia nigra induces both dopaminergic neuronal loss and

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC5871868 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature