Immunomodulatory properties of kappa opioids and synthetic cannabinoids in HIV-1 neuropathogenesis.
Immunomodulatory properties of kappa opioids and synthetic cannabinoids in HIV-1 neuropathogenesis.
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卡帕阿片类药物和合成大麻素在 HIV-1 神经发病机制中的免疫调节特性。
DOI：
10.1007/s11481-011-9306-3
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Rock,RobertBryan
中科院分区：
文献类型：
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作者：
Hu,Shuxian;Sheng,WenS;Rock,RobertBryan
抗逆转录病毒疗法（ART）对HIV-1感染者的临床结局产生了巨大影响。虽然抗逆转录病毒疗法产生了许多切实的好处，但艾滋病毒感染的慢性、长期后果也越来越重要。HIV-1相关的神经认知障碍（HAND）是一组神经系统综合征，具有广泛的功能性认知障碍。HAND仍然是对艾滋病患者的严重威胁，目前仍然没有针对HIV-1神经学表现的特异性治疗。基于在其他神经炎症模型中的工作，kappa阿片受体（KOR）和合成大麻素已被认为具有神经保护特性和抑制神经胶质细胞促炎反应的能力;这些特性可能对HIV-1神经发病机制产生积极影响。KOR配体抑制人类小胶质细胞和CD 4 T淋巴细胞中HIV-1产生的能力，表现出神经保护作用，并抑制星形胶质细胞中趋化因子的产生，这提供了令人鼓舞的数据，表明KOR配体可能成为HIV神经发病机制中的潜在治疗剂。基于合成大麻素抑制人类小胶质细胞中HIV-1表达并抑制人类星形胶质细胞中炎症介质（如一氧化氮（NO））的产生的发现，以及大量文献证明大麻素在其他系统中的神经保护特性，合成大麻素也已成为HIV神经发病机制中的潜在治疗剂。这篇综述集中在这两类化合物，并介绍了归因于每一个在艾滋病毒神经发病机制的背景下的免疫调节和神经保护特性。
Anti-retroviral therapy (ART) has had a tremendous impact on the clinical outcomes of HIV-1 infected individuals. While ART has produced many tangible benefits, chronic, long-term consequences of HIV infection have grown in importance. HIV-1-associated neurocognitive disorder (HAND) represents a collection of neurological syndromes that have a wide range of functional cognitive impairments. HAND remains a serious threat to AIDS patients, and there currently remains no specific therapy for the neurological manifestations of HIV-1. Based upon work in other models of neuroinflammation, kappa opioid receptors (KOR) and synthetic cannabinoids have emerged as having neuroprotective properties and the ability to dampen pro-inflammatory responses of glial cells; properties that may have a positive influence in HIV-1 neuropathogenesis. The ability of KOR ligands to inhibit HIV-1 production in human microglial cells and CD4 T lymphocytes, demonstrate neuroprotection, and dampen chemokine production in astrocytes provides encouraging data to suggest that KOR ligands may emerge as potential therapeutic agents in HIV neuropathogenesis. Based upon findings that synthetic cannabinoids inhibit HIV-1 expression in human microglia and suppress production of inflammatory mediators such as nitric oxide (NO) in human astrocytes, as well as a substantial literature demonstrating neuroprotective properties of cannabinoids in other systems, synthetic cannabinoids have also emerged as potential therapeutic agents in HIV neuropathogenesis. This review focuses on these two classes of compounds and describes the immunomodulatory and neuroprotective properties attributed to each in the context of HIV neuropathogenesis.