title: The emerging role of epigenetic modifications and chromatin remodeling in spinal muscular atrophy.
abstract: As the leading genetic cause for infantile death, Spinal Muscular Atrophy (SMA) has been extensively studied since its first description in the early 1890s. Though today much is known about the cause of the disease, a cure or effective treatment is not currently available. Recently the short chain fatty acid valproic acid, a drug used for decades in the management of epilepsy and migraine therapy, has been shown to elevate the levels of the essential survival motor neuron protein in cultured cells. In SMA mice, valproic acid diminished the severity of the disease phenotype. This effect was linked to the ability of the short chain fatty acid to suppress histone deacetylase activity and activate gene transcription. Since then, the study of different histone deacetylase inhibitors and their epigenetic modifying capabilities has been of high interest in an attempt to find potential candidates for effective treatment of SMA. In this review, we summarize the current knowledge about use of histone deacetylase inhibitors in SMA as well as their proposed effects on chromatin structure and discuss further implications for possible treatments of SMA arising from research examining epigenetic change.
authors.affiliation: Epigenetics in Human Health and Disease, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lunke
authors.forename: Assam
authors.initials: A
authors.lastname: El-Osta
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein; D006655:Histone Deacetylases