Mitochondrial Sirtuins in Parkinson's Disease

Abstract

Parkinson's disease (PD), the main risk factor for which is age, is one of the most common neurodegenerative diseases and imposes a substantial burden on affected individuals and the economy. While the aetiology of PD is still largely unclear, substantial evidence indicates that mitochondrial dysfunction, aggregation of α-synuclein (α-syn), oxidative stress, inflammation, and autophagy play major roles in the pathogenesis of PD. Sirtuins are NAD+-dependent protein deacetylases, includeing seven members, i.e., SIRT1-SIRT7. Among these sirtuins, SIRT3, SIRT4 and SIRT5 are located in mitochondria and are called mitochondrial sirtuins. Mitochondrial sirtuins regulate the activity and biological function of mitochondrial proteins through posttranslational modification of substrate proteins. Increasing evidence shows that mitochondrial sirtuins play an important role in degenerative diseases, including PD. Mitochondrial sirtuins exert a beneficial neuroprotective effect in various models of PD. This paper summarizes a large number of studies and discusses the latest research progress on the role of mitochondrial sirtuins in PD, focusing especially on the regulation of the mitochondrial respiratory chain (MRC), oxidative stress, the inflammatory response and autophagy, to provide new insight into the pathogenesis of PD and new targets for the diagnosis and treatment of the disease.

Keywords: Autophagy; Inflammation; Mitochondrial respiratory chain; Mitochondrial sirtuins; PD; ROS.