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HIV 的神经发病机制和新出现的治疗靶点。

Neuropathogenesis of HIV and emerging therapeutic targets.

机构信息

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Medical Education, University of Texas at Southwestern Medical School, Dallas, Tx, USA.

出版信息

Expert Opin Ther Targets. 2022 Jul;26(7):603-615. doi: 10.1080/14728222.2022.2100253. Epub 2022 Jul 18.

Abstract

INTRODUCTION

HIV infection causes a wide range of neurological complications, many of which are among the most common complications of chronic HIV infection in the era of combined antiretroviral therapy. These neurological conditions arise due to complex interactions between HIV viral proteins and neuronal and glial cells that lead to the activation of various inflammatory and neurotoxic pathways across the nervous system.

AREAS COVERED

This review summarizes the current literature on the pathogenesis and clinical manifestations of neurological injuries associated with HIV in the brain, spinal cord, and peripheral nervous system. Molecular pathways relevant for possible therapeutic targets or advancements are emphasized. Gaps in knowledge and current challenges in therapeutic design are also discussed.

EXPERT OPINION

Several challenges exist in the development of therapeutic targets for HIV-associated cognitive impairments. However, recent developments in drug delivery systems and treatment strategies are encouraging. Treatments for HIV-associated pain and peripheral sensory neuropathies currently consist of symptomatic management, but a greater understanding of their pathogenesis can lead to the development of targeted molecular therapies and disease-modifying therapies. HIV-associated autonomic dysfunction may affect the course of systemic disease via disrupted neuro-immune interactions; however, more research is needed to facilitate our understanding of how these processes present clinically.

摘要

简介

HIV 感染可引起多种神经系统并发症,其中许多是在联合抗逆转录病毒治疗时代慢性 HIV 感染最常见的并发症之一。这些神经系统疾病是由于 HIV 病毒蛋白与神经元和神经胶质细胞之间的复杂相互作用引起的,导致神经系统内各种炎症和神经毒性途径的激活。

涵盖领域

本文综述了与 HIV 相关的脑、脊髓和周围神经系统神经损伤的发病机制和临床表现的最新文献。强调了与可能的治疗靶点或进展相关的分子途径。还讨论了知识空白和当前治疗设计的挑战。

专家意见

针对 HIV 相关认知障碍的治疗靶点的开发存在一些挑战。然而,药物输送系统和治疗策略的最新进展令人鼓舞。目前,HIV 相关疼痛和周围感觉神经病变的治疗方法包括对症治疗,但对其发病机制的更深入了解可以导致针对特定分子的治疗和疾病修正治疗的发展。HIV 相关自主神经功能障碍可能会通过破坏神经免疫相互作用影响全身疾病的进程;然而,需要更多的研究来促进我们对这些过程如何在临床上表现的理解。

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