Oxidative damage in Huntington's disease.

Huntington's disease is a hereditary neurodegenerative disorder, characterized by motor, psychiatric, and cognitive symptoms. The genetic defect responsible for the onset of the disease, expansion of CAG repeats in exon 1 of the gene that codes for huntingtin, has been unambiguously identified. On the other hand, the mechanisms by which the mutation causes the disease are not completely understood yet. However, defects in the energy metabolism of affected cells may cause oxidative damage, which has been proposed as one of the underlying molecular mechanism that participates in the etiology of the disease. This chapter describes methods to genotype mice transgenic for the disease, characterizing their progressive neurological phenotype, and biochemical methods that allow determining striatal oxidative damage, and establishing the status of both protective cellular systems, and biochemical pathways that induce the generation of free radicals. The methods described in this chapter permit one to relate the neurological phenotype of the mice with the degree of oxidative damage sustained by the brain.