SIRT1 pathway in Parkinson’s disease: a faraway snapshot but so close

Abstract

AbstractSilent information regulator (SIRT) has distinctive enzymatic activities and physiological functions to control cell-cycle progression, gene expression, and DNA stability by targeting histone and non-histone proteins. SIRT1 enhances synaptic formation and synaptic activity, and therefore, can reduce the progression of various degenerative brain diseases including Parkinson’s disease (PD). SIRT1 activity is decreased by aging with a subsequent increased risk for the development of degenerative brain diseases. Inhibition of SIRT1 promotes inflammatory reactions since SIRT1 inhibits transcription of nuclear factor kappa B (NF-κB) which also inhibits SIRT1 activation via activation of microRNA and miR-34a which reduce NAD synthesis. SIRT1 is highly expressed in microglia as well as neurons, and has antioxidant and anti-inflammatory effects. Therefore, this review aimed to find the possible role of SIRT1 in PD neuropathology. SIRT1 has neuroprotective effects; therefore, downregulation of SIRT1 during aging promotes p53 expression and may increase the vulnerability of neuronal cell deaths. PD neuropathology is linked with the sequence of inflammatory changes and the release of pro-inflammatory cytokines due to the activation of inflammatory signaling pathways. In addition, oxidative stress, inflammatory disorders, mitochondrial dysfunction, and apoptosis contribute mutually to PD neuropathology. Thus, SIRT1 and SIRT1 activators play a crucial role in the mitigation of PD neuropathology through the amelioration of oxidative stress, inflammatory disorders, mitochondrial dysfunction, apoptosis, and inflammatory signaling pathways.