Focal nature of neurological disorders necessitates isotype-selective histone deacetylase (HDAC) inhibitors.
Histone deacetylase (HDAC) inhibitors represent a promising new avenue of therapeutic options for a range of neurological disorders. Within any particular neurological disorder, neuronal damage or death is not widespread; rather, particular brain regions are preferentially affected. Different disorders exhibit distinct focal pathologies. Hence, understanding the region-specific effects of HDAC inhibitors is essential for targeting appropriate brain areas and reducing toxicity in unaffected areas. The outcome of HDAC inhibition depends on several factors, including the diversity in the central nervous system expression of HDAC enzymes, selectivity of a given HDAC inhibitor for different HDAC enzymes, and the presence or absence of cofactors necessary for enzyme function. This review will summarize brain regions associated with various neurological disorders and factors affecting the consequences of HDAC inhibition.
Thomas
Elizabeth A
EA
Department of Molecular Biology, The Scripps Research Institute, MB-10, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA. bthomas@scripps.edu
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005786:Gene Expression Regulation; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D009422:Nervous System Diseases / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D007527:Isoenzymes; D006655:Histone Deacetylases