Insights Into the Therapeutic Potential of SIRT1-modifying Compounds for Alzheimer’s Disease: A Focus on Molecular Mechanisms

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, significantly impacting patients’ quality of life. Recent studies have highlighted the roles of sirtuin 1 (SIRT1), a NAD + -dependent deacetylase, in regulating various biological pathways associated with AD pathology, including amyloid-beta metabolism, tau hyperphosphorylation, and neuroinflammation. This review focuses on the therapeutic potential of synthetic and natural compounds that modulate SIRT1 levels, emphasizing their molecular mechanisms of action. We explore a range of SIRT1-modifying agents, including polyphenols such as resveratrol, as well as synthetic analogs and novel pharmaceuticals that aim to enhance SIRT1 activity. Additionally, we discuss emerging innovative therapies, including pharmacological agents that improve SIRT1 signaling through mechanisms like photobiomodulation and nutritional interventions. These compounds not only target SIRT1 but also integrate into broader metabolic and neuroprotective pathways, presenting a promising approach to ameliorating AD symptoms. By elucidating the intricate interactions between SIRT1-modifying compounds and their effects on AD pathology, this review aims to advance the understanding of potential therapeutic strategies that could delay or prevent the progression of AD.