HIV, Tat and dopamine transmission.
HIV, Tat and dopamine transmission.
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DOI：
10.1016/j.nbd.2017.04.015
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发表时间：
2017-09
影响因子：
6.1
通讯作者：
Khoshbouei H
中科院分区：
文献类型：
--
作者：
Gaskill PJ;Miller DR;Gamble-George J;Yano H;Khoshbouei H
人类免疫缺陷病毒（HIV）是一种以免疫系统为目标的进行性感染，影响着全球3700多万人。虽然抗逆转录病毒联合疗法（cART）降低了感染者的死亡率并改善了生活质量，但与艾滋病毒相关的神经认知障碍的患病率正在上升，与艾滋病毒相关的认知能力下降仍然普遍存在。最近的研究表明，HIV辅助蛋白可能参与了这种下降，并且一些研究表明，HIV蛋白转录反激活因子（Tat）可以破坏正常的神经元和神经胶质功能。具体来说，数据表明，Tat可能通过调节多巴胺转运体的功能和特异性损害中枢神经系统富含多巴胺的区域，直接影响多巴胺能神经传递。HIV感染的中枢神经系统长期以来一直与多巴胺能功能障碍有关，但其机制尚不明确。Tat对多巴胺能神经传递的特殊作用可能是HIV感染直接或间接诱导多巴胺能功能障碍的一种机制。因此，精确定义Tat对多巴胺能系统的具体作用将有助于阐明HIV感染中枢神经系统诱导涉及多巴胺能神经传递的神经精神、神经认知和神经系统疾病的机制。此外，这将提供进一步这些调查所需的实验的讨论，并可能有助于确定或开发新的治疗方法，以预防或治疗艾滋病毒感染者的这些疾病。
Human Immunodeficiency Virus (HIV) is a progressive infection that targets the immune system, affecting more than 37 million people around the world. While combinatorial antiretroviral therapy (cART) has lowered mortality rates and improved quality of life in infected individuals, the prevalence of HIV associated neurocognitive disorders is increasing and HIV associated cognitive decline remains prevalent. Recent research has suggested that HIV accessory proteins may be involved in this decline, and several studies have indicated that the HIV protein transactivator of transcription (Tat) can disrupt normal neuronal and glial function. Specifically, data indicate that Tat may directly impact dopaminergic neurotransmission, by modulating the function of the dopamine transporter and specifically damaging dopamine-rich regions of the CNS. HIV infection of the CNS has long been associated with dopaminergic dysfunction, but the mechanisms remain undefined. The specific effect(s) of Tat on dopaminergic neurotransmission may be, at least partially, a mechanism by which HIV infection directly or indirectly induces dopaminergic dysfunction. Therefore, precisely defining the specific effects of Tat on the dopaminergic system will help to elucidate the mechanisms by which HIV infection of the CNS induces neuropsychiatric, neurocognitive and neurological disorders that involve dopaminergic neurotransmission. Further, this will provide a discussion of the experiments needed to further these investigations, and may help to identify or develop new therapeutic approaches for the prevention or treatment of these disorders in HIV-infected individuals.
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DOI：
10.1076/jcen.25.7.893.16489
发表时间：
2003-10-01
影响因子：
2.2
作者：
Basso, MR;Bornstein, RA
通讯作者：
Bornstein, RA
影响因子：
3.2
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影响因子：
4.4
作者：
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通讯作者：
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影响因子：
6.1
作者：
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通讯作者：
Marvel, Cherie L.
影响因子：
4.8
作者：
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Chetrit J