Sirtuin deacetylases as therapeutic targets in the nervous system.

Abstract

Sirtuins are a conserved family of deacetylases whose activities are dependent on nicotinamide adenine dinucleotide (NAD+). Sirtuins act in different cellular compartments, such as the nucleus where they deacetylate histones and transcriptional factors, in the cytoplasm where they modulate cytoskeletal and signaling molecules, and in the mitochondria where they engage components of the metabolic machinery. Collectively, they tune metabolic processes to energy availability, and modulate stress responses, protein aggregation, inflammatory processes, and genome stability. As such, they have garnered much interest and have been widely studied in aging and age-related neurodegeneration. In this chapter, we review the identification of sirtuins and their biological targets. We focus on their biological mechanisms of action and how they might be regulated, including via NAD metabolism, transcriptional and posttranscriptional control, and as targets of pharmacological agents. Lastly, we highlight the numerous studies suggesting that sirtuins are efficacious therapeutic targets in neurodegenerative disease and injury.

• Authors: Brett Langley, Anthony Sauve
• Journal: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics (Neurotherapeutics) Vol. 10 Issue 4 Pg. 605-20 (Oct 2013) ISSN: 1878-7479 [Electronic] United States
• PMID: 24037427 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Group III Histone Deacetylases
• Sirtuins

Topics

• Cell Nucleus (genetics, metabolism)
• Gene Expression Regulation
• Group III Histone Deacetylases (genetics, metabolism)
• Humans
• Mitochondria (genetics, metabolism)
• Nervous System Diseases (genetics, metabolism, therapy)
• Sirtuins (genetics, metabolism)