Endoplasmic reticulum stress and autophagy in HIV-1-associated neurocognitive disorders
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REVIEW
Endoplasmic reticulum stress and autophagy in HIV-1-associated neurocognitive disorders Xue Chen 1 & Tong Zhang 1 & Yulin Zhang 1 Received: 28 May 2020 / Revised: 24 July 2020 / Accepted: 28 August 2020 # Journal of NeuroVirology, Inc. 2020
Abstract 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. Keywords HIV-1 associated neurocognitive disorders . Endoplasmic reticulum stress . Autophagy . Pathogenesis . Targeted therapy
Introduction HIV-1-associated neurocognitive disorders (HAND) are a serious complication of AIDS. Although the emergence of antiretroviral therapy (ART) has improved the survival rate of HIV patients, the incidence of HAND remains approximately between 20–50% and thus seriously affects the patients’ quality of life (Robertson et al. 2007). However, the pathogenesis of HAND has yet to be fully clarified due to its complexity. Indeed, the mechanisms underlying the onset of HAND may involve multiple pathways, including the destruction of the blood-brain barrier (BBB) (Kanmogne et al. 2006), excitotoxicity, oxidative stress, mitochondrial dysfunction,
* Tong Zhang [email protected] * Yulin Zhang [email protected] 1
Department of Infectious Diseases, Beijing You An Hospital, Beijing Institute of Hepatology, Capital Medical University, Beijing 100069, China
calcium maladjustment, and signal changes (Kragh et al. 2012). Moreover, there is no cure for HAND, and the strict adherence to ART to maintain a low viral load in the blood remains the only treatment (Churchill et al. 2016). The pathologies of many neurodegenerative diseases, including HAND and Alzheimer’s disease (AD), are related to the progressive accumulation of misfolded proteins and insufficient clearance rate of such proteins in the brains of infected individuals: a component of the pathogenesis of HAND from which the entire
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