hdac inhibitors in neurodegenerative disorders

neurodegenerative disorders such as huntingtons disease, alzheimers disease, parkinsons 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 them, 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. during the past six years, numerous studies identified histone deacetylase (hdac) inhibitors as candidate drugs for the treatment of neurodegenerative disorders. two major neuroprotective mechanisms of hdac inhibitors have been identified, namely the transcriptional activation of disease-modifying genes and the correction of perturbations in histone acetylation homeostasis, which have been shown to be intimately involved in the neurodegenerative pathomechanisms of huntingtons, parkinsons and kennedy disease, amyotrophic lateral sclerosis, rubinstein-taybi syndrome and stroke. based on the promising in vitro and in vivo analyses, clinical trials have been initiated to evaluate the safety and efficacy of hdac inhibitors for the treatment of devastating diseases such as huntingtons disease, amyotrophic lateral sclerosis and spinal muscular atrophy. we will discuss most of the recent applications of hdac inhibitors in the cited neurodegenerative disorders and share with you our knowledge of the involvement of singular hdac/sirt isoform in neurodegenerative disorders and other cns pathologies.