The role of oxidative stress in HIV-associated neurocognitive disorders

Brain, Behavior, & Immunity - Health

Melissa J. Churchill¹  Jacob D. Estes²  Thomas A. Angelovich³  Stavros Selemidis⁴  Sarah Byrnes⁴  Michael Roche⁴  Sarah Buckley⁴  Catherine Cochrane⁴ 

[1] Science University, United States;The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia;;Vaccine and Gene Therapy Institute, Oregon National Primate Research Centre, Oregon Health &Chronic Infectious and Inflammatory Diseases Program, School of Health and Biomedical Sciences, RMIT University, Melbourne, Australia;

关键词: HIV;    HAND;    Oxidative stress;    ROS;    ART;    Neurodegeneration;   

DOI  :  

来源: DOAJ

【 摘 要 】

HIV-associated neurocognitive disorders (HAND) are a leading cause of morbidity in up to 50% of individuals living with HIV, despite effective treatment with antiretroviral therapy (ART). Current evidence suggests that chronic inflammation associated with HIV is especially attributed to the dysregulated production of reactive oxygen species (ROS) that contribute to neurodegeneration and poor clinical outcomes. While ROS have beneficial effects in eliciting immune responses to infection, chronic ROS production causes damage to macromolecules such as DNA and lipids that has been linked to altered redox homeostasis associated with antioxidant dysregulation. As a result, this disruption in the balance between antioxidant-dependent mechanisms of ROS inactivation and ROS production by enzymes such as the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family, as well as from the electron transport chain of the mitochondria can result in oxidative stress. This is particularly relevant to the brain, which is exquisitely susceptible to oxidative stress due to its inherently high lipid concentration and ROS levels that have been linked to many neurodegenerative diseases that have similar stages of pathogenesis to HAND. In this review, we discuss the possible role and mechanisms of ROS production leading to oxidative stress that underpin HAND pathogenesis even when HIV is suppressed by current gold-standard antiretroviral therapies. Furthermore, we highlight that pathological ROS can serve as biomarkers for HIV-dependent HAND, and how manipulation of oxidative stress and antioxidant-dependent pathways may facilitate novel strategies for HIV cure.

【 授权许可】

Unknown