SIRT1 and neuronal diseases.
SIRT1 is the mammalian homologue of yeast silent information regulator (Sir)-2, a member of the sirtuin family of protein deacetylases which have gained much attention as mediators of lifespan extension in several model organisms. Induction of SIRT1 expression also attenuates neuronal degeneration and death in animal models of Alzheimer's disease and Huntington's disease. SIRT1 induction, either by sirtuin activators such as resveratrol, or metabolic conditioning associated with caloric restriction (CR), could be neuroprotective in several ways. It could promote the non-amyloidogenic cleavage of the amyloid precursor protein, enhance clearance of amyloid beta-peptides, and reduced neuronal damage through potential inhibition of neuroinflammatory signaling pathways. In addition, increased SIRT1 activity could alter neuronal transcription profiles to enhance anti-stress and anti-apoptotic gene activities, and has been proposed to underlie the inhibition of axonal degeneration in the Wallerian degeneration slow (Wld(s)) phenotype. As neuronal degeneration is a major pathophysiological aspect of human aging, understanding the mechanism of SIRT1 neuroprotection promises novel strategies in clinical intervention of neurodegenerative diseases.
Tang
Bor Luen
BL
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore. bchtbl@nus.edu.sg
Chua
Christelle En Lin
CE
D000818:Animals; D002470:Cell Survival; D006801:Humans; D050505:Mutant Proteins / Q000378:metabolism; D009422:Nervous System Diseases / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D037761:Sirtuins / Q000378:metabolism*
D050505:Mutant Proteins; D037761:Sirtuins