Modulatory Effects of Nicotine on neuroHIV/neuroAIDS.
Modulatory Effects of Nicotine on neuroHIV/neuroAIDS.
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DOI：
10.1007/s11481-018-9806-5
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Li MD
中科院分区：
文献类型：
--
作者：
Han H;Yang Z;Chang SL;Li MD
尼古丁是烟草烟雾中的关键活性成分之一，通过与尼古丁乙酰胆碱受体（nAChRs）结合发挥作用。尽管在许多动物和人体研究中都显示了尼古丁的消极和积极药理作用，但其与人类免疫缺陷病毒-1 （HIV-1）的相互作用尚未完全阐明。尽管联合抗逆转录病毒治疗（cART）限制了HIV-1向获得性免疫缺陷综合征（AIDS）的进展，但hiv相关的神经认知障碍（HAND）仍然普遍存在。因此，迫切需要加强我们对手相关神经功能障碍的理解。HAND与阿尔茨海默病（AD）或帕金森病（PD）有一些共同的生化途径和生理功能障碍，尼古丁可能在HAND中发挥与AD和PD相同的神经保护作用。在过去的十几年中，在体内和体外研究中，尼古丁的各种潜在治疗作用，如神经保护作用，已经被揭示出来，包括使用HIV-1转基因（HIV-1Tg）大鼠模型，模拟接受cART的hiv感染患者。本文综述了吸烟和不吸烟的HIV/AIDS患病率的最新进展，一些研究HIV-1感染相关神经功能障碍的动物模型，阐明吸烟/尼古丁对HIV/AIDS的调节作用，尼古丁的抗炎作用，以及在HIV- 1tg大鼠模型中观察到的神经保护作用。综上所述，这些发现表明：尽管吸烟确实会对健康和疾病状况（如艾滋病毒感染）造成有害影响，但烟草烟雾的重要成分尼古丁已被证明对艾滋病毒患者具有一定的神经保护作用，可能是通过其抗炎作用。因此，有必要研究尼古丁对神经艾滋病毒/神经艾滋病的双重影响，以期更好地确定尼古丁或其类似物的潜在医疗用途，并使其以更纯净、更危险的形式提供。吸烟是艾滋病毒/艾滋病的一种具有挑战性的共病。尼古丁作为烟草烟雾的关键成分，对免疫系统和认知都有一定的调节作用。尼古丁的神经保护作用在阿尔茨海默病和帕金森病中都有特点，它可能类似地参与保护hiv -1感染者，特别是对HAND的感染。尼古丁的神经保护作用已经在一些HIV-1动物模型中得到了很好的证明，特别是HIV-1Tg大鼠，因此需要进一步的研究来描述尼古丁的潜在医学用途，研究尼古丁对HAND的保护作用的分子和细胞机制，并最终提供临床策略来降低艾滋病感染者的吸烟率。
Nicotine, one of the key active ingredients in tobacco smoke, exerts its effects via binding to nicotinic acetylcholine receptors (nAChRs). Although both negative and positive pharmacological effects of nicotine have been shown in numerous animals and human studies, its interaction with human immunodeficiency virus-1 (HIV-1) have not been fully elucidated. Even though combined anti-retroviral therapy (cART) limits the progression of HIV-1 to acquired immune deficiency syndrome (AIDS), HIV-associated neurocognitive disorders (HAND) remain prevalent. There is thus a compelling need to enhance our understanding of HAND-related neurologic dysfunction. Some biochemical pathways and physiological dysfunctions have been found to be shared by HAND and Alzheimer’s (AD) or Parkinson’s (PD) diseases, and nicotine may exert the same neuroprotection in HAND that has been observed in both AD and PD. In the past dozen years, various potential therapeutic effects of nicotine such as neuroprotection have been revealed in both in vivo and in vitro studies, including using HIV-1 transgenic (HIV-1Tg) rat model, which mimics HIV-infected patients receiving cART. In the current review, we describe recent progress in the prevalence of HIV/AIDS with and without cigarette smoking, some animal models for studying neural dysfunction associated with HIV-1 infection, elucidating the modulatory effects of cigarette smoking/nicotine on HIV/AIDS, the anti-inflammatory effects of nicotine, and the neuroprotective effects observed in HIV-1Tg rat model. Taken together, these findings suggest the following: although tobacco smoking does cause deleterious effects in both health and disease conditions such as HIV infection, nicotine, the significant component of tobacco smoke, has been shown to possess some neuroprotective effects in HIV patients, possible via its anti-inflammatory activities. It is therefore necessary to study nicotine’s dual effects on neuroHIV/neuroAIDS in hope of better defining the potential medical uses of nicotine or its analogues, and to make them available in a purer and less dangerous form. Cigarette smoking is a challenging comorbidity to HIV/AIDS. Nicotine, as a key component of tobacco smoke, has some modulatory effects on both the immune system and cognition. Nicotine’s neuroprotective effects have been characterized in both AD and PD, and it may be involved similarly in protecting HIV-1–infected individuals, especially against HAND. Neuroprotective effects of nicotine have been well demonstrated using some HIV-1 animal models, particularly the HIV-1Tg rats, further studies are therefore needed to delineate the potential medical uses of nicotine, to study molecular and cellular mechanisms underlying nicotine’s protective effects against HAND, and finally to provide clinical strategies to reduce the rate of cigarette smoking among the PLWHA.
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