Novel gene (TMEM230) linked to Parkinson’s disease

摘要

Mutations in six genes are known to cause Parkinson’s disease (PD) (autosomal dominant: alpha-synuclein, LRRK2, VPS35 and autosomal recessive: Parkin, PINK1 and DJ1) and number of other genes are implicated. In a recent article Deng and colleagues studied a large four generation American family of European descent and linked mutations in a novel gene, transmembrane-protein 230 gene (TMEM230) with lewy body confirmed PD. The authors demonstrated that pathogenic TMEM230 variants in primary mouse neurons affected movement of synaptic vesicles suggesting that TMEM230 may slow vesicular transport. Further experiments in HEK293 cells (carrying the pathogenic TMEM230 variants) showed increased alpha-synuclein levels. This study indicated that the impaired vesicular trafficking may contribute to the pathogenesis of PD. Understanding the various cellular mechanisms leading to PD may lead to the development of novel, much needed therapeutic options. These mechanisms could include: enhanced clearance of damaged mitochondria, development of kinase inhibitors, VPS35/retromer function enhancers or now the possibility of vesicular transport modification.