Oxidative stress in Huntington's disease

It has been five years since the elucidation of the genetic mutation underl ying the pathogenesis of Huntington's disease (HD) (97), however the precis e mechanism of the selective neuronal death it propagates still remains an enigma, Several different etiological processes may play roles, and strong evidence from studies in both humans and animal models suggests the involve ment of energy metabolism dysfunction, excitotoxic processes, and oxidative stress. Importantly, the recent development of transgenic mouse models of HD led to the identification of neuronal intranuclear inclusion bodies in a ffected brain regions in both mouse models and in HD brain, consisting of p rotein aggregates containing fragments of mutant huntingtin protein. These observations opened new avenues of investigation into possible huntingtin p rotein interactions and their putative pathogenetic sequelae, Amongst these studies, findings of elevated levels of oxdative damage products such as m alondialdehyde, 8-hydroxy-deoxyguanosine, 3-nitrotyrosine and heme oxygenas e in areas of degeneration in HD brain, and of increased free radical produ ction in animal models, indicate the involvement of oxidative stress either as a causative event, or as a secondary constituent of the cell death casc ade in the disease, Here we review the evidence for oxidative damage and po tential mechanisms of neuronal death in HD.