Glutaminase-containing microvesicles from HIV-1-infected macrophages and immune-activated microglia induce neurotoxicity
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- 作者：Beiqing Wu ; Yunlong Huang ; Alexander L. Braun ; Zenghan Tong…
- 关键词：HAND ; HIV ; Glutamate ; Glutaminase ; Microvesicles ; Neurotoxicity
- 刊名：Molecular Neurodegeneration
- 出版年：2015
- 出版时间：December 2015
- 年：2015
- 卷：10
- 期：1
- 全文大小：2,907 KB
- 刊物主题：Neurosciences; Neurology; Molecular Medicine;
- 出版者：BioMed Central
- ISSN：1750-1326
文摘
Background HIV-1-infected and/or immune-activated microglia and macrophages are pivotal in the pathogenesis of HIV-1-associated neurocognitive disorders (HAND). Glutaminase, a metabolic enzyme that facilitates glutamate generation, is upregulated and may play a pathogenic role in HAND. Our previous studies have demonstrated that glutaminase is released to the extracellular fluid during HIV-1 infection and neuroinflammation. However, key molecular mechanisms that regulate glutaminase release remain unknown. Recent advances in understanding intercellular trafficking have identified microvesicles (MVs) as a novel means of shedding cellular contents. We posit that during HIV-1 infection and immune activation, microvesicles may mediate glutaminase release, generating excessive and neurotoxic levels of glutamate.