Targeting the correct HDAC(s) to treat cognitive disorders.
Changes in gene expression in the brain may underlie cognitive deficits inherent to normal aging and neurodegenerative disease. However, the mechanisms underlying pathological alterations in the brain transcriptome are incompletely understood. Epigenetic mechanisms such as DNA methylation and histone acetylation have been shown to be important for memory processes in the adult brain. There is accumulating evidence that altered chromatin plasticity and histone acetylation are also involved in cognitive aging, neurodegeneration, and neuropsychiatric diseases. Inhibitors of histone deacetylase (HDAC) exhibit neuroprotective and neuroregenerative properties in animal models of various brain diseases. As such, targeting of HDACs seems to be a promising therapeutic strategy. In this review, we discuss the specific roles of each HDAC protein and the possible function of distinct histone modifications. We hope that this knowledge will aid in the development of diagnostic tools and in designing more potent and specific treatment for neurological disorders targeting selective HDAC proteins.
Fischer
André
A
Laboratory for Aging and Cognitive Diseases, European Neuroscience Institute, Grisebach Str. 5, D-37077 Goettingen, Germany. afische2@gwdg.de
Sananbenesi
Farahnaz
F
Mungenast
Alison
A
Tsai
Li-Huei
LH
D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D044127:Epigenesis, Genetic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000187:drug effects / Q000378:metabolism; D006801:Humans
D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases