Therapeutic potential of sirtuin-activating compounds in Alzheimer's disease.
Sirtuins, known as silent information regulators, are class III histone deacetylases (HDAC) that catalyze deacetylation reaction in an NAD(+)-dependent manner. Evolutionarily conserved from bacteria to humans, sirtuins regulate important cell functions by deacetylating histone and nonhistone targets. Activation of sirtuin extends lifespan and promotes longevity and healthy aging in a variety of species, potentially delaying the onset of age-related neurodegenerative disorders. In mammalian systems, sirtuin activators protect against axonal degeneration, poly-glutamine toxicity and microglia-mediated amyloid beta toxicity, suggesting the potential therapeutic value of sirtuins in patients with neurodegenerative diseases, such as Alzheimer's disease. In this review, we discuss the potential role of the sirtuin pathway in modifying the pathogenic processes in Alzheimer's disease.
Gan
Li
L
Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158, USA. lgan@gladstone.ucsf.edu
D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D031204:Caloric Restriction; D004789:Enzyme Activation / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008928:Mitochondria / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D037761:Sirtuins / Q000502:physiology*
D016229:Amyloid beta-Peptides; D037761:Sirtuins