AMPK activation leads to SIRT-1 activation by increasing NAD/NADH ratio, promoting autophagy and upregulated the expression of the autophagy-related gene beclin-1, leading to enhanced clearance of aggregated misfolded α-syn and subsequently suppressing neuronal apoptosis while promoting neuronal survival and improving locomotor function in PD [118,119,120] Importantly, the clearance of accumulated misfolded α-syn through enhanced autophagy may alleviate ER stress and return ER homeostasis, resulting in the suppression of neuronal apoptosis in dopaminergic neurons [121]. The gene discussed is SIRT1; the disease is Parkinson disease.