Sirtuins as Novel Targets for Alzheimer's Disease and Other Neurodegenerative Disorders: Experimental and Genetic Evidence

Abstract

Sirtuins are a family of conserved proteins with deacetylase and ADP-ribosyltransferase activity. In humans they are coded by seven genes (SIRT1-7). The most widely investigated and best known sirtuin is SIRT1, which can be activated by the natural phytocompound resveratrol and plays a role in several physiologic (embryogenesis, glucose metabolism, apoptosis, autophagy, chromatin integrity, and transcriptional state) and pathologic (diabetes, cancer, cardiovascular disorders, and neurodegeneration) conditions. In the field of neurodegeneration, resveratrol and SIRT1 have proved beneficial in in vitro and in vivo models of Alzheimer's disease (AD), reducing amyloid-beta protein accumulation, considered one of the pathogenic mechanisms. In contrast to these promising biological data, however, genetic studies linking SIRT1 variability to AD are negative (this is the case for other sirtuins too, e.g., SIRT3). In this review, we summarize the in vitro, in vivo, and genetic experimental results linking SIRT1 and the other sirtuins to AD, while a description of sirtuins' biochemical features and modulating compounds, as well as sirtuins' involvement in other neurodegenerative disorders are discussed as collateral aims.