Journal
CELL RESEARCH
Volume 23, Issue 6, Pages 746-758Publisher
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2013.70
Keywords
sirtuin; histone deacetylase; Alzheimer's disease; Parkinson's disease; Huntington's disease; amyotrophic lateral sclerosis; spinal and bulbar muscular atrophy
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Funding
- NIA NIH HHS [R37 AG011119, R01 AG015339, R56 AG015339] Funding Source: Medline
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Sirtuin enzymes are a family of highly conserved protein deacetylases that depend on nicotinamide adenine dinucleotide (NAD+) for their activity. There are seven sirtuins in mammals and these proteins have been linked with caloric restriction and aging by modulating energy metabolism, genomic stability and stress resistance. Sirtuin enzymes are potential therapeutic targets in a variety of human diseases including cancer, diabetes, inflammatory disorders and neurodegenerative disease. Modulation of sirtuin activity has been shown to impact the course of several aggregate-forming neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and spinal and bulbar muscular atrophy. Sirtuins can influence the progression of neurodegenerative disorders by modulating transcription factor activity and directly deacetylating proteotoxic species. Here, we describe sirtuin protein targets in several aggregate-forming neurodegenerative diseases and discuss the therapeutic potential of compounds that modulate sirtuin activity in these disorders.
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