Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Review
MeSH terms
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Acetylation
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Alzheimer Disease / drug therapy
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Alzheimer Disease / enzymology
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Alzheimer Disease / physiopathology
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Amyotrophic Lateral Sclerosis / drug therapy
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Amyotrophic Lateral Sclerosis / enzymology
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Amyotrophic Lateral Sclerosis / physiopathology
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Animals
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Disease Models, Animal
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Histone Deacetylase Inhibitors / therapeutic use*
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Histone Deacetylases / metabolism*
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Histones / metabolism
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Humans
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Huntington Disease / drug therapy
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Huntington Disease / enzymology
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Huntington Disease / physiopathology
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Muscular Atrophy, Spinal / drug therapy
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Muscular Atrophy, Spinal / enzymology
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Muscular Atrophy, Spinal / physiopathology
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Neurodegenerative Diseases / drug therapy
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Neurodegenerative Diseases / enzymology*
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Neurodegenerative Diseases / pathology
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Neurodegenerative Diseases / physiopathology
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Neuroprotective Agents / classification
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Neuroprotective Agents / therapeutic use
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Parkinson Disease / drug therapy
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Parkinson Disease / enzymology
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Parkinson Disease / physiopathology
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Rats
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Stroke / drug therapy
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Stroke / enzymology
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Stroke / physiopathology
Substances
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Histone Deacetylase Inhibitors
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Histones
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Neuroprotective Agents
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Histone Deacetylases