The delicate balance between neurotoxicity and neuroprotection in the context of HIV-1 infection.,Glia

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The delicate balance between neurotoxicity and neuroprotection in the context of HIV-1 infection.
Glia ( IF 5.4 ) Pub Date : 2020-09-10 , DOI: 10.1002/glia.23904
Vincent Sénécal ₁ , Corinne Barat ₁ , Michel J Tremblay _{1,

2}

Affiliation

Human immunodeficiency virus type‐1 (HIV‐1) causes a spectrum of neurological impairments, termed HIV‐associated neurocognitive disorder (HAND), following the infiltration of infected cells into the brain. Even though the implementation of antiretroviral therapy reduced the systemic viral load, the prevalence of HAND remains unchanged and infected patients develop persisting neurological disturbances affecting their quality of life. As a result, HAND have gained importance in basic and clinical researches, warranting the need of developing new adjunctive treatments. Nonetheless, a better understanding of the molecular and cellular mechanisms remains necessary. Several studies consolidated their efforts into elucidating the neurotoxic signaling leading to HAND including the deleterious actions of HIV‐1 viral proteins and inflammatory mediators. However, the scope of these studies is not sufficient to address all the complexity related to HAND development. Fewer studies focused on an altered neuroprotective capacity of the brain to respond to HIV‐1 infection. Neurotrophic factors are endogenous polyproteins involved in neuronal survival, synaptic plasticity, and neurogenesis. Any defects in the processing or production of these crucial factors might compose a risk factor rendering the brain more vulnerable to neuronal damages. Due to their essential roles, they have been investigated for their diverse interplays with HIV‐1 infection. In this review, we present a complete description of the neurotrophic factors involved in HAND. We discuss emerging concepts for their therapeutic applications and summarize the complex mechanisms that down‐regulate their production in favor of a neurotoxic environment. For certain factors, we finally address opposing roles that rather lead to increased inflammation.

中文翻译：

在 HIV-1 感染的情况下，神经毒性和神经保护之间的微妙平衡。

人类免疫缺陷病毒 1 型 (HIV-1) 在感染细胞渗入大脑后会导致一系列神经损伤，称为 HIV 相关神经认知障碍 (HAND)。尽管抗逆转录病毒疗法的实施降低了全身病毒载量，但 HAND 的患病率保持不变，受感染的患者会出现持续的神经障碍，影响他们的生活质量。因此，HAND 在基础和临床研究中变得越来越重要，因此需要开发新的辅助治疗方法。尽管如此，仍然有必要更好地了解分子和细胞机制。几项研究巩固了他们的努力，以阐明导致 HAND 的神经毒性信号，包括 HIV-1 病毒蛋白和炎症介质的有害作用。然而，这些研究的范围不足以解决与 HAND 发育相关的所有复杂性。很少有研究关注大脑对 HIV-1 感染做出反应的神经保护能力的改变。神经营养因子是参与神经元存活、突触可塑性和神经发生的内源性多蛋白。这些关键因素的加工或生产中的任何缺陷都可能构成一个风险因素，使大脑更容易受到神经元损伤。由于它们的重要作用，已经研究了它们与 HIV-1 感染的多种相互作用。在这篇综述中，我们对 HAND 中涉及的神经营养因子进行了完整的描述。我们讨论了它们治疗应用的新兴概念，并总结了下调它们的产生以有利于神经毒性环境的复杂机制。对于某些因素，我们最终解决了导致炎症增加的相反作用。

更新日期：2020-09-10

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