Validation of Sirtuin 3 as a Neuroprotective and Neurorestorative Target in the Mutant Human A53T α-synuclein Rat Model of Parkinson’s Disease

Mitochondrial dysfunction plays a major role in the progressive and pathological development of Parkinson’s disease (PD). Mitochondrial protein deacetylase sirtuin 3 (SIRT3) assists in controlling bioenergetic and antioxidation processes by regulating mitochondrial enzyme acetylation levels. Based on this, overexpression of SIRT3 in the substantia nigra pars compacta (SNc) was assessed for its disease-modifying and cytoprotective effects in a well-accepted, adeno-associated virus (AAV) model of PD. SIRT3-myc AAV was infused into the SNc before or after A53T AAV induction of parkinsonism and analyzed at three and six-week time points. Results suggested that at six weeks, SIRT3 overexpression significantly reduced parkinsonian deficits, localized to the mitochondria, and displayed deacetylase function. Overall, the beneficial effects of SIRT3 demonstrate its disease-modifying implications for PD.M.Sc