Histone deacetylase inhibitors: possible implications for neurodegenerative disorders.
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 Huntington's, Parkinson's and Kennedy disease, amyotropic lateral sclerosis, Rubinstein-Taybi syndrome as well as 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 Huntington's disease, amyotropic lateral sclerosis and spinal muscular atrophy. Here, the authors summarize and discuss the findings on the emerging field of epigenetic therapy strategies in neurodegenerative disorders.
Hahnen
Eric
E
Institute of Human Genetics, Institute of Genetics, University of Cologne, 50931 Cologne, Germany. eric.hahnen@uk-koeln.de
Hauke
Jan
J
Tränkle
Christian
C
Eyüpoglu
Ilker Y
IY
Wirth
Brunhilde
B
Blümcke
Ingmar
I
D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000326:Adrenoleukodystrophy / Q000188:drug therapy / Q000235:genetics; D000818:Animals; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D012415:Rubinstein-Taybi Syndrome / Q000188:drug therapy / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism
C431694:ABCD2 protein, human; D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters; D056572:Histone Deacetylase Inhibitors; D010455:Peptides; C097188:polyglutamine; D006655:Histone Deacetylases