Steiner Joseph, Haughey Norman, Li Wenxue, Venkatesan Arun, Anderson Caroline, Reid Rollie, Malpica Tanya, Pocernich Chava, Butterfield D Allan, Nath Avindra
Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.
Antioxid Redox Signal. 2006 Nov-Dec;8(11-12):2089-100. doi: 10.1089/ars.2006.8.2089.
Despite the rapidly increasing incidence of HIV infection worldwide and the increasing prevalence of HIVassociated cognitive impairment, even in patients adequately treated with antiretroviral therapy, currently no effective treatment exists for HIV dementia. A broad range of studies using either brain or cerebrospinal fluid (CSF) tissues from well-characterized patients with HIV dementia, animal models, and in vitro studies from several laboratories using HIV-infected cells or HIV proteins provide overwhelming evidence for oxidative stress in mediating neuronal injury in this patient population. These studies also suggest that patients with apolipoprotein E (ApoE) 4 allele are more susceptible to such oxidative damage. In this review, we provide a critical analysis of these studies, including the few clinical trials that have used antioxidants to treat HIV dementia. We also discuss several novel agents with potent antioxidative properties and provide a rationale for combination antioxidant and neuroprotective therapy.
尽管全球范围内HIV感染的发病率迅速上升，且与HIV相关的认知障碍患病率不断增加，即使是接受抗逆转录病毒疗法充分治疗的患者，目前仍没有针对HIV痴呆的有效治疗方法。一系列研究使用来自特征明确的HIV痴呆患者的大脑或脑脊液（CSF）组织、动物模型，以及多个实验室使用HIV感染细胞或HIV蛋白进行的体外研究，为氧化应激介导该患者群体的神经元损伤提供了压倒性的证据。这些研究还表明，携带载脂蛋白E（ApoE）4等位基因的患者更容易受到这种氧化损伤。在这篇综述中，我们对这些研究进行了批判性分析，包括少数使用抗氧化剂治疗HIV痴呆的临床试验。我们还讨论了几种具有强大抗氧化特性的新型药物，并为抗氧化剂与神经保护联合治疗提供了理论依据。
