Genetics and Molecular Biology of Parkinson Disease

Parkinson disease (PD) is one of the most common neurodegenerative disorders. Over the past 15. years, several genes have been identified that cause PD in a Mendelian fashion, or act as susceptibility factors. Study of the protein products encoded by these genes and the pathogenetic effect related to specific mutations has greatly improved our understanding of PD, indicating many cellular pathways that, when impaired, lead to neurodegeneration. In particular, mitochondrial dysfunction and alterations in intracellular clearance mechanisms such as autophagy and the ubiquitin-proteasome system result in oxidative stress and accumulation of misfolded proteins/damaged organelles, and represent critical processes in the etiology of both familiar and sporadic PD.