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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Histone Deacetylation and Motor Neuron Degeneration

Author(s): S. Schmalbach and S. Petri

Volume 9, Issue 3, 2010

Page: [279 - 284] Pages: 6

DOI: 10.2174/187152710791292684

Price: $65

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with progressive muscular wasting and paralysis due to loss of motor neurons in the primary motor cortex, brainstem and spinal cord. Alterations of transcriptional activity due to an unbalance of the activity of histone acetyl transferases (HAT) and histone deacetylases (HDACs) have been described in a variety of neurodegenerative conditions in vitro and in vivo. HDACs can be grouped into four different classes with distinct cellular localization and functions. HDAC inhibitors have recently been discovered as potential neuroprotective drugs for the treatment of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). A major limitation, however, lies in the broad spectrum of action of currently available HDAC inhibitors causing a variety of toxic side effects.

Keywords: Amyotrophic lateral sclerosis, neurodegeneration, transcriptional regulation, histone deacetylases, HDAC inhibitors, sirtuins


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