人类免疫缺陷病毒促进线粒体毒性。
Human Immunodeficiency Virus Promotes Mitochondrial Toxicity.
机构信息
Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd NW, Washington, DC, 20057, USA.
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
出版信息
Neurotox Res. 2017 Nov;32(4):723-733. doi: 10.1007/s12640-017-9776-z. Epub 2017 Jul 10.
Abstract
Combined antiretroviral therapies (cART) have had remarkable success in reducing morbidity and mortality among patients infected with human immunodeficiency virus (HIV). However, mild forms of HIV-associated neurocognitive disorders (HAND), characterized by loss of synapses, remain. cART may maintain an undetectable HIV RNA load but does not eliminate the expression of viral proteins such as trans-activator of transcription (Tat) and the envelope glycoprotein gp120 in the brain. These two viral proteins are known to promote synaptic simplifications by several mechanisms, including alteration of mitochondrial function and dynamics. In this review, we aim to outline the many targets and pathways used by viral proteins to alter mitochondria dynamics, which contribute to HIV-induced neurotoxicity. A better understanding of these pathways is crucial for the development of adjunct therapies for HAND.
摘要
联合抗逆转录病毒疗法（cART）在降低感染人类免疫缺陷病毒（HIV）患者的发病率和死亡率方面取得了显著成功。然而，仍存在 HIV 相关神经认知障碍（HAND）的轻度形式，其特征是突触丧失。cART 可以保持 HIV RNA 载量不可检测，但不能消除病毒蛋白如转录激活物（Tat）和包膜糖蛋白 gp120 在大脑中的表达。这两种病毒蛋白已知通过多种机制促进突触简化，包括改变线粒体功能和动力学。在这篇综述中，我们旨在概述病毒蛋白用于改变线粒体动力学的许多靶点和途径，这些途径有助于 HIV 引起的神经毒性。更好地了解这些途径对于 HAND 的辅助治疗的发展至关重要。
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