Silent Information Regulator 1/Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α Axis: A Promising Target for Parkinson's and Alzheimer's Disease Therapies

Abstract

One of the key challenges in medical research is developing safe medications to treat neurodegenerative disorders. Increased oxidative stress, mitochondrial dysfunction, and neuroinflammation are common features of Alzheimer's disease (AD) and Parkinson's disease (PD). Silent information regulator 1 (SIRT-1), part of the sirtuin family, plays a critical role in various physiological processes by binding to histones and nonhistone proteins. SIRT-1 primarily mitigates oxidative stress and regulates mitochondrial activity by maintaining the deacetylated form of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), ensuring stable PGC-1α levels. Research has shown reduced SIRT-1/PGC-1α expression in AD and PD models. Targeting this pathway presents a promising therapeutic approach for managing AD and PD, potentially leading to disease-modifying treatments and improved outcomes. This review highlights the findings of various studies suggesting that the SIRT-1/PGC-1α pathway promotes mitochondrial biogenesis, synaptic plasticity, and cognitive function, as well as exerts antioxidant, anti-inflammatory, and anti-apoptotic effects, offering a potential method for AD and PD treatment.