Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders.
Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders.
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DOI：
10.1007/s00018-021-03785-y
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Meucci O
中科院分区：
文献类型：
--
作者：
Irollo E;Luchetta J;Ho C;Nash B;Meucci O
HIV相关神经认知障碍（HAND）的特征是HIV感染者的认知和行为缺陷。HAND在接受抗逆转录病毒治疗的患者中仍然很常见，尽管他们往往表现出不太严重的症状。接受治疗的患者中HAND的持续流行是一个重大的治疗挑战，因为即使是轻微的认知障碍也会降低患者的生活质量。因此，现代HAND研究旨在扩大我们对艾滋病毒感染者认知障碍机制的理解，并确定有希望的分子途径和可用于治疗的靶点。最近的研究表明，治疗患者的HAND至少部分是由轻微的突触树突损伤和介导学习、记忆和执行功能的脑区神经元网络的破坏引起的。虽然微妙的神经元功能障碍的原因是多种多样的，在动物模型中逆转突触树突损伤恢复认知功能，从而突出了一个有前途的治疗方法。在这篇综述中，我们研究的证据，突触树突状细胞损伤和中断神经元连接的手从临床神经影像学和神经病理学研究，并讨论研究的手模型，定义结构和功能障碍的神经传递。然后，我们报告了参与这种神经元功能障碍的分子通路、机制和共病，讨论了逆转神经元损伤的新方法，并强调了目前的知识空白。如果我们要开发安全有效的治疗方法来逆转微妙的神经病理学和认知障碍，那么继续研究HAND患者和实验模型中突触损伤和网络功能障碍的表现和机制将是至关重要的。
HIV-associated neurocognitive disorder (HAND) is characterized by cognitive and behavioral deficits in people living with HIV. HAND is still common in patients that take antiretroviral therapies, although they tend to present with less severe symptoms. The continued prevalence of HAND in treated patients is a major therapeutic challenge, as even minor cognitive impairment decreases patient’s quality of life. Therefore, modern HAND research aims to broaden our understanding of the mechanisms that drive cognitive impairment in people with HIV and identify promising molecular pathways and targets that could be exploited therapeutically. Recent studies suggest that HAND in treated patients is at least partially induced by subtle synaptodendritic damage and disruption of neuronal networks in brain areas that mediate learning, memory, and executive functions. Although the causes of subtle neuronal dysfunction are varied, reversing synaptodendritic damage in animal models restores cognitive function and thus highlights a promising therapeutic approach. In this review, we examine evidence of synaptodendritic damage and disrupted neuronal connectivity in HAND from clinical neuroimaging and neuropathology studies and discuss studies in HAND models that define structural and functional impairment of neurotransmission. Then, we report molecular pathways, mechanisms, and comorbidities involved in this neuronal dysfunction, discuss new approaches to reverse neuronal damage, and highlight current gaps in knowledge. Continued research on the manifestation and mechanisms of synaptic injury and network dysfunction in HAND patients and experimental models will be critical if we are to develop safe and effective therapies that reverse subtle neuropathology and cognitive impairment.
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影响因子：
9.9
作者：
Ances, B. M.;Christensen, J. J.;Clifford, D. B.
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