UNC5C Receptor Proteolytic Cleavage by Active AEP Promotes Dopaminergic Neuronal Degeneration in Parkinson's Disease.

ABSTRACT: Netrin-1 is a chemotropic cue mediating axon growth and neural migration in neuronal development, and its receptors deletion in colorectal cancer and UNC5s act as dependence receptors regulating neuronal apoptosis. Asparagine endopeptidase (AEP) is an age-dependent protease that cuts human alpha-synuclein (α-Syn) at N103 and triggers its aggregation and neurotoxicity. In the current study, it is reported that UNC5C receptor is cleaved by AEP in Parkinson's disease (PD) and facilitates dopaminergic neuronal loss. UNC5C is truncated by active AEP in human α-SNCA transgenic mice in an age-dependent manner or induced by neurotoxin rotenone. Moreover, UNC5C is fragmented by AEP in PD brains, inversely correlated with reduced netrin-1 levels. Netrin-1 deprivation in primary cultures induces AEP

SUBMITTER: Chen G 

PROVIDER: S-EPMC8895126 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature