Mocchetti Italo, Bachis Alessia, Masliah Eliezer
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
J Neurosci Res. 2008 Feb 1;86(2):243-55. doi: 10.1002/jnr.21492.
Chemokine receptors, in particular, CXCR4 and CCR5, mediate human immunodeficiency virus type 1 (HIV-1) infection of immunocompetent cells and the apoptosis of these cells. However, the virus does not infect neurons. Yet through a variety of mechanisms, HIV promotes glial cell activation, synaptodendritic alterations, and neuronal loss that ultimately lead to motor and cognitive impairment. Chemokines and chemokine receptors are abundant in the adult central nervous system and play a role in neuronal apoptosis evoked by HIV proteins. Thus, reducing the availability of chemokine receptors may prevent the neuronal degeneration seen in HIV-positive patients. In this article, we present and discuss a recent experimental approach aimed at testing effective neuroprotective therapies against HIV-mediated neuronal degeneration.
趋化因子受体,尤其是CXCR4和CCR5,介导1型人类免疫缺陷病毒(HIV-1)对免疫活性细胞的感染以及这些细胞的凋亡。然而,该病毒并不感染神经元。不过,HIV通过多种机制促进神经胶质细胞活化、突触树突改变以及神经元丧失,最终导致运动和认知障碍。趋化因子和趋化因子受体在成体中枢神经系统中大量存在,并在HIV蛋白诱发的神经元凋亡中发挥作用。因此,减少趋化因子受体的可利用性可能会预防HIV阳性患者出现的神经元变性。在本文中,我们展示并讨论了一种旨在测试针对HIV介导的神经元变性的有效神经保护疗法的最新实验方法。