Nef在hiv相关神经认知障碍中的多方面作用:组织病理学改变和潜在机制。

IF 2.8 3区 医学 Q3 NEUROSCIENCES
Grazia Scuderi, Paolo Fagone, Maria Cristina Petralia, Ferdinando Nicoletti, Maria Sofia Basile
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引用次数: 0

摘要

尽管抗逆转录病毒疗法能够持久地抑制人类免疫缺陷病毒(HIV)的复制,但艾滋病毒感染者发生慢性合并症的风险仍然增加,例如艾滋病毒相关神经认知障碍(HAND)。在缺乏明确的生物标志物或治愈性治疗的情况下,HAND影响了多达50%的艾滋病毒感染者的生存和生活质量。因此,新的策略非常有必要改善HAND患者的诊断、监测和治疗,而对HAND发病机制的更深入了解是实现这一目标的基础。HAND的发病、进展和临床结局受多种因素的影响,包括病毒蛋白如阴性因子(Nef)。在HIV蛋白中,Nef是HAND发病的潜在关键因素。Nef可以驱动大脑特定的组织病理改变,并可能通过不同的相互关联的病理机制参与HAND。这些包括:免疫失调、氧化应激、线粒体功能障碍、自噬破坏、髓磷脂损伤和少突胶质细胞功能障碍、血脑屏障破坏、胆固醇稳态改变以及与阿尔茨海默病相关的某些潜在趋同机制。细胞外和细胞内的Nef都可以促进HAND的发展。有趣的是,有人提出Nef可能通过结合到细胞外囊泡参与HAND。这篇综述探讨了Nef在HAND中的多方面作用,强调了组织病理学改变和可能涉及的发病机制,以及Nef作为HAND诊断和治疗靶点的潜在相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Multifaceted Role of Nef in HIV-Associated Neurocognitive Disorder: Histopathological Alterations and Underlying Mechanisms.

Although antiretroviral regimens achieve durable suppression of human immunodeficiency virus (HIV) replication, individuals living with HIV remain at an increased risk of developing chronic comorbidities, such as HIV-associated neurocognitive disorder (HAND). In the absence of definitive biomarkers or curative treatments, HAND impacts the survival and quality of life in up to 50% of individuals with HIV. Therefore, novel strategies are highly warranted to improve the diagnosis, monitoring, and treatment of individuals with HAND and a deeper characterization of the still poorly understood pathogenesis of HAND is fundamental to this aim. The pathogenesis, progression, and clinical outcomes of HAND are influenced by different factors, including viral proteins like negative factor (Nef). Among HIV proteins, Nef emerges as a potential key contributor to HAND pathogenesis. Nef could drive specific histopathological alterations in the brain and could be involved in HAND through different interconnected pathogenetic mechanisms. These include: immune dysregulation, oxidative stress, mitochondrial dysfunction, disruption of autophagy, myelin damage and oligodendrocytes dysfunction, blood-brain barrier disruption, alterations of cholesterol homeostasis, and certain potential converging mechanisms with Alzheimer's disease. Both extracellular and intracellular Nef can contribute to the development of HAND. Interestingly, it has been proposed that Nef may participate in HAND through its incorporation into extracellular vesicles. This review explores the multifaceted role of Nef in HAND, highlighting the histopathological alterations and the pathogenetic mechanisms potentially involved and the potential emerging relevance of Nef as a diagnostic and therapeutic target in HAND.

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来源期刊
Brain Sciences
Brain Sciences Neuroscience-General Neuroscience
CiteScore
4.80
自引率
9.10%
发文量
1472
审稿时长
18.71 days
期刊介绍: Brain Sciences (ISSN 2076-3425) is a peer-reviewed scientific journal that publishes original articles, critical reviews, research notes and short communications in the areas of cognitive neuroscience, developmental neuroscience, molecular and cellular neuroscience, neural engineering, neuroimaging, neurolinguistics, neuropathy, systems neuroscience, and theoretical and computational neuroscience. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.
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