Narendra Lab

 

Our group studies inherited movement disorders with a focus on the genetics and molecular pathogenesis of Early Onset Parkinson’s Disease (EOPD) (onset at 50 years or before). Whereas idiopathic Parkinson’s disease is typically sporadic, EOPD is frequently caused by mutation(s) in a single gene. Many of the genes responsible for EOPD have been identified. The relationship among these genes in the molecular pathogenesis of Parkinson’s disease, however, remains ill-defined. We recently discovered that two of these genes, Parkin and PINK1, function in a novel mitochondrial quality control pathway in which impaired mitochondria are targeted for lysosomal degradation by mitophagy (a selective form of macroautophagy). Interestingly, two other genes causing EOPD, DJ-1 and the recently identified CHCHD2, share with Parkin and PINK1 a role in mitochondrial biology, suggesting commonalities in pathogenesis. To characterize the molecular pathogenesis of EOPD, we use a combination of novel genetic tools, advanced imaging methods like super-resolution microscopy, quantitative proteomics, and biochemical studies in cellular and mouse models. Additionally, we are collecting DNA samples and fibroblasts from patients with EOPD to better assess the contribution of known genes to the risk of EOPD and to uncover new causes of EOPD, using exome sequencing. It is our hope that these studies will ultimately clarify the