Author: Greene J.G.

Source: Current Neuropharmacology, Volume 2, Number 3, July 2004 , pp. 331-342(12)

Publisher: Bentham Science Publishers

Abstract:

Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder for which there is no known cure. In the years since the discovery of a trinucleotide CAG repeat in the gene encoding huntingtin as the disease's causative genetic lesion, there has been an explosion of research attempting to elucidate the mechanisms of neurodegeneration in HD, with the ultimate goal being the development of effective neuroprotective therapy. Development of genetic models of the disorder has been instrumental in these advances, and combination of these with established toxic models has made significant headway in delineating mechanisms of neuronal dysfunction and death in HD. Established theories of pathogenesis, such as mitochondrial dysfunction and glutamate excitotoxicity have been linked with more recently explored mechanisms of damage, such as abnormal programmed cell death, transcriptional dysregulation, and protein aggregation to develop a more unified theory of HD pathogenesis. These investigations have revealed a complex web of pathways that may trigger and shape neuronal death in HD. Discovery of this neuronal death machinery has afforded a great opportunity to intervene to prevent neuronal death at many potential targets that have synergistic mechanisms of action. Continued aggressive research should eventually develop a cure for this devastating disease.

Keywords: huntington disease; huntingtin; neuroprotection; polyglutamine; mitochondria; excitotoxicity; apoptosis; protein aggregation

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1570159043359620

Affiliations: 1: Departments of Neurology and Pharmacology and Center for Neurodegenerative Diseases, Emory University School of Medicine, 5002 Rollins Research Building, 1510 Clifton Road, Atlanta, GA 30322, USA

Publication date: 2004-07-01

More about this publication?

• Current Neuropharmacology aims to provide current, timely and comprehensive reviews of all areas of neuropharmacology and related matters of neuroscience. The journal publishes reviews written by experts and leaders in the fields of molecular, cellular, and systems/behavioural aspects of neuropharmacology and neuroscience. The journal serves as a comprehensive, multidisciplinary expert forum for neuropharmacologists and neuroscientists.

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