The neurobiology of sirtuins and their role in neurodegeneration.

Sirtuins are highly conserved NAD(+)-dependent enzymes that have beneficial effects against age-related diseases. Aging is the major unifying risk factor for all neurodegenerative disorders. Sirtuins modulate major biological pathways, such as stress response, protein aggregation, and inflammatory processes, that are involved in age-related neurodegenerative diseases. Therefore, sirtuins have been widely studied in the context of the nervous system and neurodegeneration. They are especially interesting because it is possible to alter the activities of sirtuins using small molecules that could be developed into drugs. Indeed, it has been shown that manipulation of SIRT1 activity genetically or pharmacologically impacts neurodegenerative disease models. This review summarizes recent research in sirtuin neurobiology and neurodegenerative diseases and analyzes the potential of therapeutic applications based on sirtuin research.