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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Histone Deacetylase Inhibitors: Therapeutic Agents and Research Tools for Deciphering Motor Neuron Diseases

Author(s): A. Echaniz-Laguna, O. Bousiges, J.-P. Loeffler and A.-L. Boutillier

Volume 15, Issue 13, 2008

Page: [1263 - 1273] Pages: 11

DOI: 10.2174/092986708784534974

Price: $65

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Abstract

Histone deacetylase (HDAC) inhibition as a therapeutic regimen in motor neuron diseases (MND) is generating intense interest in both the scientific and medical areas, with a number of potent compounds having demonstrated good safety profiles and hints of clinical activity on animal models. In this review, we discuss recent developments in dissecting the mechanism of action of HDAC inhibitors (HDACi) as a new group of mechanism-based drugs for motor neuron diseases, together with current progress in understanding their clinical application. We also discuss how the use of HDACi on animal models with motor neuron defects has allowed critical advances in the understanding of the pathophysiology of motor neuron diseases. The use of HDACi and possible mechanisms of action will be reviewed in three MND, i.e. amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and spinal and bulbar muscular atrophy (SBMA), diseases among which clinical trials with HDACi are currently perfomed (ALS, SMA).

Keywords: Motor neuron diseases, Histone deacetylases inhibitors, acetylation, transcription, neuronal death, epigenetic regulations


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