Oxidative Stress in Huntington's Disease

Abstract

Although the pathogenesis of the neurodegenerative phenomena of Huntington's disease (HD) is not well known, in the last 30 years, numerous data have been published that suggest a possible role of oxidative stress. The majority of studies regarding this issue were performed in different experimental models of this disease (neurotoxic models such as intraperitoneal injection of 3-nitropropionic acid or intrastriatal injection of quinolinic acid, transgenic animal models for HD, and cell cultures) and, less frequently, in samples of brain tissue, plasma/serum, blood cells, and other tissues from patients with a genetic-molecular diagnosis of presymptomatic and symptomatic HD compared to healthy controls. In this narrative review, we have summarized the data from the main studies in which oxidative stress parameters have been measured both in patients with HD and in experimental models of the same disease, as well as the few studies on gene variants involved in oxidative stress in patients with HD. Most studies addressing this issue in experimental models of HD have shown an increase in markers or oxidative stress, a decrease in antioxidant substances, or both. However, the results of studies on patients with HD have not been conclusive as few studies have been published on the matter. However, a meta-analysis of blood studies on HD patients (including a pool of serum and blood cell studies) has shown an increase in lipid peroxidation markers, OH8dG concentrations, and GPx activity and a decrease in GSH levels. Future prospective and multicenter studies with a long-term follow-up period involving a large number of HD patients and healthy controls are needed to address this topic.

Keywords: Huntington’s disease; animal models; biological markers; oxidative stress; pathogenesis.

Figure 1

Possible interactions between the different pathogenic mechanisms proposed for Huntington’s disease.

Figure 2

Summary of the most important changes related to oxidative stress reported in Huntington’s disease patients and experimental models of Huntington’s disease.