Autophagy and Its Association with Genetic Mutations in Parkinson Disease

Parkinson disease is the second most common neurodegenerative disorder, affecting 0.1-0.2% of the general population. It is a progressive debilitating disorder caused by degeneration of dopaminergic neurons in the substantia nigra pars compacta. It is characterized by motor and non-motor symptoms. Parkinson disease can be caused by mutations in genes that encode proteins involved in the autophagic process, resulting in impaired autophagy. Indeed, autophagy has been implicated in the pathogenesis of Parkinson disease, particularly because its impairment causes the buildup of proteins. Thus, this review aims to provide an overview of Parkinson disease-related genetic mutations and their association with autophagy impairment in Parkinson disease, which can be helpful in improving the understanding of the pathogenesis of Parkinson disease, illustrating the potential therapeutic implications of agents that can enhance autophagy in Parkinson disease. Additionally, we will highlight the essential need for the development of highly sensitive and specific assays for gene-based diagnostic biomarkers. Finally, we will provide an overview on the potential gene-based therapeutic approaches for Parkinson disease, which have been most advanced and are associated with the most common targets being alpha-synuclein (SNCA), leucine-rich repeat kinase-2 (LRRK2), and glucocerebrosidase (GBA).