Molecular insights into Parkinson's disease

Abstract

Mutations in SNCA, PINK1, parkin, and DJ-1 are associated with autosomal-dominant or autosomal-recessive forms of Parkinson's disease (PD), the second most common neurodegenerative disorder. Studies on the structural and functional properties of the corresponding gene products have provided significant insights into the molecular underpinnings of familial PD and the much more common sporadic forms of the disease. Here, we review recent advances in our understanding of four PD-related gene products: α-synuclein, parkin, PINK1, and DJ-1. In Part 1, we review new insights into the role of α-synuclein in PD. In Part 2, we summarize the latest developments in understanding the role of mitochondrial dysfunction in PD, emphasizing the role of the PINK1/parkin pathway in regulating mitochondrial dynamics and mitophagy. The role of DJ-1 is also discussed. In Part 3, we point out converging pathways and future directions.