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

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

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986708784534974

Affiliations: Department of Neurology, Hopital Civil de Strasbourg, 1 Place de l'Hopital, BP426, 67091 Strasbourg, France.

Publication date: June 1, 2008

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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