Histone Deacetylase Inhibitors and Neurodegenerative Disorders: Holding the Promise

Antonello      Mai; Dante      Rotili; Sergio      Valente; Aleksey   G.   Kazantsev

Abstract

Neurodegenerative disorders (NDs) such as Huntingtons disease, Alzheimers disease, Parkinson disease, amyotrophic lateral sclerosis, spinal muscular atrophy, Friedreichs ataxia, and others are multi-factorial illnesses, in which many pathways (still poorly understood) act serially and in parallel to give a determined pathologic phenotype. Thus, presently there are no effective cures for these diseases. Some phenotypic as well as mechanistic features, common to the most of NDs, can be linked to epigenetic defects, that can lead to alteration of acetylation homeostasis and impairment of the histone acetyltransferase (HAT): histone deacetylase (HDAC) balance. Here we survey most of the recent applications of HDAC inhibitors in the cited NDs, and we make the point of our (up to now) knowledge about the involvement of singular HDAC/SIRT isoform in NDs and other CNS pathologies.

Keywords: Epigenetics, HDAC inhibitors, neurodegenerative disorders, Huntington's disease, Alzheimer's disease, Parkinson disease, amyotrophic lateral sclerosis, spinal muscular atrophy, Friedreich's ataxia