Potential Role of Sirtuin as a Therapeutic Target for Neurodegenerative Diseases

The sirtuins (SIRTs) are protein-modifying enzymes that are distributed ubiquitously in all organisms. SIRT1 is a mammalian homologue of yeast nicotinamide-adenine-dinucleotide-dependent deacetylase silent informnation regulator 2 (known as Sir2), which is the best-characterized SIRT family member. It regulates longevity in several model organisms and is involved in several processes in mammalian cells including cell survival, differentiation, and metabolism. SIRT1 induction, either by SIRT-activating compounds such as resveratrol, or metabolic conditioning associated with caloric restriction, could have neuroprotective qualities and thus delay the neurodegenerative process, thereby promoting longevity. However, the precise mechanistic liaison between the activation of SIRT and extended healthy aging or delaying age-related diseases in humans has yet to be established. J Clin Neurol 2009;5:120-125