The effect of Puerarin on 3-Nitropropionic acid-induced neurotoxicity.

Abstract

Huntington disease (HD) is an incurable, adult-onset, autosomal dominant inherited disorder. HD is named after George Huntington, the physician who described it as hereditary chorea in 1872. Characteristic features of HD include jerky, random, involuntary movements called chorea. Patients also may have some behavioral and psychiatric problems. Patients may present with one or all disorders in varying degrees. Physical symptoms of HD can begin at any age from infancy to old age, but usually begin be-tween 35 and 44 years of age. If symptoms begin before about 20 years of age, they progress faster and vary slightly, and the disease is classified as juvenile HD. Many reports suggest that neuromodultion, oxidative stress, apoptosis and neuroinflammation plays a key role in the pathogenesis of HD. Experimental models have begun to uncover these pathways, thus helping to understand the mechanisms implicated and allowing for the characteri-zation of potential targets for new therapeutic strategies. 3-Nitropropionic acid is known to produce behavioral, biochemical and morphologic changes similar to those occurring in HD. 3-Nitropropionic acid, which resembles the substrate succinate, irreversibly binds to succinate dehydro-genase (SDH) and inhibits its activity in the citric acid cycle, ultimately interfering with ATP synthesis, and gives rise to free radicals, both nitric oxide (NO) and reactive oxygen species (ROS), thus resulting in metabolic compromise that involves three interacting processes: energy impairment, excitotoxicity, and oxidative stress. Oxidative stress and excitotoxicity are two conditions leading to cell death, by both necrosis and apoptosis.