Huntington's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Huntington's Disease, including details on genetics, causes, symptoms, treatment.

3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington's disease.

Brouillet E, Jacquard C, Bizat N, Blum D

Centre Nationale de la Recherche Scientifique 2210, Service Hospitalier Frédéric Joliot, Départment de Recherches Médicales, Direction des Sciences du Vivant, CEA, Orsay France. brouille@shfj.cea.fr

Huntington's disease (HD) is a neurodegenerative disorder caused by a mutation in the gene encoding Huntingtin. The mechanisms underlying the preferential degeneration of the striatum, the most striking neuropathological change in HD, are unknown. Of those probably involved, mitochondrial defects might play an important role. The behavioural and anatomical similarities found between HD and models using the mitochondrial toxin 3-nitropropionic acid (3NP) in rats and primates support this hypothesis. Here, we discuss the recently identified mechanisms of 3NP-induced striatal degeneration. Two types of important factor have been identified. The first are the 'executioner' components that have direct roles in cell death, such as c-Jun N-terminal kinase and Ca2+-activated protease calpains. The second are 'environmental' factors, such as glutamate, dopamine and adenosine, which modulate the striatal degeneration induced by 3NP. Interestingly, these recent studies support the hypothesis that 3NP and mutated Huntingtin have certain mechanisms of toxicity in common, suggesting that the use of 3NP might give new insights into the pathogenesis of HD. Research on 3NP provides additional proof that the neurochemical environment of a given neurone can determine its preferential vulnerability in neurodegenerative diseases.

Published 20 December 2005 in J Neurochem, 95(6): 1521-40.
Full-text of this article is available online (may require subscription).

© 2005-2008 Huntington's Disease Research Today. All Rights Reserved.