Multiple roles of HDAC inhibition in neurodegenerative conditions.
Histone deacetylases (HDACs) play a key role in homeostasis of protein acetylation in histones and other proteins and in regulating fundamental cellular activities such as transcription. A wide range of brain disorders are associated with imbalances in protein acetylation levels and transcriptional dysfunctions. Treatment with various HDAC inhibitors can correct these deficiencies and has emerged as a promising new strategy for therapeutic intervention in neurodegenerative disease. Here, we review and discuss intriguing recent developments in the use of HDAC inhibitors to combat neurodegenerative conditions in cellular and disease models. HDAC inhibitors have neuroprotective, neurotrophic and anti-inflammatory properties; improvements in neurological performance, learning/memory and other disease phenotypes are frequently seen in these models. We discuss the targets and mechanisms underlying these effects of HDAC inhibition and comment on the potential for some HDAC inhibitors to prove clinically effective in the treatment of neurodegenerative disorders.
Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive MSC 1363, Bethesda, MD 20892-1363, USA. chuang@mail.nih.gov
De-Maw
DM
Chuang
Yan
Y
Leng
Zoya
Z
Marinova
Hyeon-Ju
HJ
Kim
Chi-Tso
CT
Chiu
D000107:Acetylation; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D009134:Muscular Atrophy, Spinal / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000145:classification / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D051381:Rats; D020521:Stroke / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology
D056572:Histone Deacetylase Inhibitors; D006657:Histones; D018696:Neuroprotective Agents; D006655:Histone Deacetylases