Endoplasmic reticulum stress and autophagy in HIV-1-associated neurocognitive disorders

Although antiretroviral therapy (ART) affects virologic suppression and prolongs life expectancies among HIV-positive patients; HIV-1-associated neurocognitive disorders (HAND) continue to be diagnosed in patients with HIV-1 undergoing treatment. The extensive clinical manifestations of HAND include behavioral, cognitive, and motor dysfunctions that severely affect the patients' quality of life. The pathogenesis of HAND has received increasing attention as a potential avenue by which to improve the treatment of the condition. Many studies have shown that endoplasmic reticulum (ER) stress, autophagy, and their interaction play important roles in the onset and development of neurodegenerative diseases. While the accumulation of misfolded proteins can induce ER stress, autophagy can effectively remove accumulated toxic proteins, reduce ER stress, and thus inhibit the development of neuropathy. Through the in-depth study of ER stress and autophagy, both have been recognized as promising targets for pharmacotherapeutic intervention in the treatment of HAND. This review will highlight the effects of ER stress, autophagy, and their interaction in the context of HAND, thereby helping to inform the future development of targeted treatments for patients with HAND.