The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders.
The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders.
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DOI：
10.3389/fmicb.2015.01164
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发表时间：
2015
影响因子：
5.2
通讯作者：
Valente ST
中科院分区：
文献类型：
--
作者：
Mediouni S;Marcondes MC;Miller C;McLaughlin JP;Valente ST
抗逆转录病毒疗法显著改善了人类免疫缺陷病毒1（HIV-1）感染者的生活。尽管如此，艾滋病毒相关的神经认知障碍（HAND），从无法检测到的神经认知障碍到严重的痴呆症，仍然影响着大约50%的感染人群，影响着他们的生活质量。HAND的持续存在是由几个因素促进的，包括较长的预期寿命、中枢神经系统（CNS）中的病毒残留水平以及HIV-1调节蛋白如转录的反式激活因子（达特）在脑中的持续存在。达特是一种分泌的病毒蛋白，其穿过血脑屏障进入CNS，在CNS中其具有直接作用于神经元和非神经元细胞的能力。这些作用导致炎症、氧化应激和兴奋性毒性中涉及的可溶性因子的释放，最终导致神经元损伤。与一般人群相比，HIV-1阳性人群中甲基苯丙胺（MA）滥用者的比例较高。另一方面，MA滥用与病毒复制增加、Tat介导的神经毒性增强和神经认知障碍相关。虽然已经研究了几种策略来减少HAND和MA的使用，但目前尚无临床批准的治疗方法。本文就达特和MA在HAND中的作用的最新研究结果进行综述，并讨论一些有前景的潜在治疗进展。
Antiretroviral therapy has dramatically improved the lives of human immunodeficiency virus 1 (HIV-1) infected individuals. Nonetheless, HIV-associated neurocognitive disorders (HAND), which range from undetectable neurocognitive impairments to severe dementia, still affect approximately 50% of the infected population, hampering their quality of life. The persistence of HAND is promoted by several factors, including longer life expectancies, the residual levels of virus in the central nervous system (CNS) and the continued presence of HIV-1 regulatory proteins such as the transactivator of transcription (Tat) in the brain. Tat is a secreted viral protein that crosses the blood–brain barrier into the CNS, where it has the ability to directly act on neurons and non-neuronal cells alike. These actions result in the release of soluble factors involved in inflammation, oxidative stress and excitotoxicity, ultimately resulting in neuronal damage. The percentage of methamphetamine (MA) abusers is high among the HIV-1-positive population compared to the general population. On the other hand, MA abuse is correlated with increased viral replication, enhanced Tat-mediated neurotoxicity and neurocognitive impairments. Although several strategies have been investigated to reduce HAND and MA use, no clinically approved treatment is currently available. Here, we review the latest findings of the effects of Tat and MA in HAND and discuss a few promising potential therapeutic developments.