Involvement of casein kinase 1 epsilon/delta (Csnk1e/d) in the pathogenesis of familial Parkinson's disease caused by CHCHD2.

ABSTRACT: Parkinson's disease (PD) is a common neurodegenerative disorder that results from the loss of dopaminergic neurons. Mutations in coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) gene cause a familial form of PD with α-Synuclein aggregation, and we here identified the pathogenesis of the T61I mutation, the most common disease-causing mutation of CHCHD2. In Neuro2a cells, CHCHD2 is in mitochondria, whereas the T61I mutant (CHCHD2^T61I ) is mislocalized in the cytosol. CHCHD2^T61l then recruits casein kinase 1 epsilon/delta (Csnk1e/d), which phosphorylates neurofilament and α-Synuclein, forming cytosolic aggresomes. In vivo, both Chchd2^T61I knock-in and transgenic mice display neurodegenerative phenotypes and aggresomes containing Chchd2^T61I

SUBMITTER: Torii S 

PROVIDER: S-EPMC10493588 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature