Department of Pathology, School of Dental Medicine, University of Pennsylvania, 240 S. 40th St, Room 312 Levy Building, Philadelphia, PA 19104-6030, USA.
J Neuroimmune Pharmacol. 2010 Sep;5(3):294-309. doi: 10.1007/s11481-010-9205-z. Epub 2010 Apr 16.
Human immunodeficiency virus type 1 (HIV) infection presently affects more that 40 million people worldwide, and is associated with central nervous system (CNS) disruption in at least 30% of infected individuals. The use of highly active antiretroviral therapy has lessened the incidence, but not the prevalence of mild impairment of higher cognitive and cortical functions (HIV-associated neurocognitive disorders) as well as substantially reduced a more severe form dementia (HIV-associated dementia). Furthermore, improving neurological outcomes will require novel, adjunctive therapies that are targeted towards mechanisms of HIV-induced neurodegeneration. Identifying such molecular and pharmacological targets requires an understanding of the events preceding irreversible neuronal damage in the CNS, such as actions of neurotoxins (HIV proteins and cellular factors), disruption of ion channel properties, synaptic damage, and loss of adult neurogenesis. By considering the specific mechanisms and consequences of HIV neuropathogenesis, unified approaches for neuroprotection will likely emerge using a tailored, combined, and non-invasive approach.
人类免疫缺陷病毒 1 型（HIV）感染目前影响全球超过 4000 万人，并与中枢神经系统（CNS）紊乱相关，至少 30%的感染者存在这种情况。高效抗逆转录病毒疗法的应用降低了发病率，但并未降低轻度认知和皮质功能障碍（HIV 相关性认知障碍）的发生率，也未能显著降低更严重形式的痴呆（HIV 相关性痴呆）的发生率。此外，要改善神经学结果，就需要针对 HIV 诱导的神经退行性变机制的新型辅助治疗方法。确定此类分子和药理学靶点需要了解 CNS 中不可逆神经元损伤之前发生的事件，如神经毒素（HIV 蛋白和细胞因子）的作用、离子通道特性的破坏、突触损伤和成年神经发生的丧失。通过考虑 HIV 神经发病机制的具体机制和后果，使用量身定制、联合和非侵入性的方法，很可能会出现针对神经保护的统一方法。
