Gp120-Mediated Cell Death in the Basal Ganglia

Gp120 介导的基底神经节细胞死亡

• 批准号: 6879144
• 负责人: Rachel Lauren Nosheny
• 金额: $ 2.74万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6879144
• 关键词: AIDS dementia complex; HIV envelope protein gp120; HIV infections; RNase protection assay; acetylcholine; apoptosis; basal ganglia; behavior test; biological signal transduction; brain derived neurotrophic factor; cell type; colorimetry; cytokine receptors; dementia; gamma aminobutyrate; high performance liquid chromatography; immunocytochemistry; interneurons; laboratory rat; neuroprotectants; neurotoxins; predoctoral investigator; protein structure function; receptor expression; terminal nick end labeling

DESCRIPTION (provided by applicant): More than 50% of human immunodeficiency virus type 1 (HIV-1) infected individuals experience neurological and psychiatric problems that are collectively termed the AIDS Dementia Complex (ADC). The current global AIDS crisis highlights the need for therapeutic strategies to treat ADC. A wealth of experimental data has implicated glycoprotein gpl20, an HIV-derived envelope protein that facilitates viral entry into cells, in the cell death associated with ADC. Clinical observations of ADC patients, in vitro characterization of cell types vulnerable to gp 120 neurotoxicity, and preliminary in vivo data in our laboratory suggest that basal ganglia dysfunction, especially of the nigro-striatal pathway, is integral to the neurological manifestations in ADC. Neurotrophic factors are naturally occurring proteins that are essential for brain development and maintenance of neuronal populations affected in ADC. The proposed experiments will examine the hypothesis that gp 120 causes cell death in the basal ganglia and that neurotrophic factors can protect against gp 120-mediated cell death. This neuroprotection in turn may limit neurological complications associated with HIV infection in the brain.

描述（由申请人提供）：超过50％的人类免疫缺陷病毒1型（HIV-1）感染的个体经历了神经和精神病患者，这些问题统称为艾滋病痴呆症复合体（ADC）。当前的全球艾滋病危机凸显了需要治疗ADC的治疗策略的必要性。大量的实验数据暗示了糖蛋白GPL20是一种艾滋病毒衍生的包膜蛋白，可促进与ADC相关的细胞死亡中病毒进入细胞。对ADC患者的临床观察，在实验室中容易受到GP 120神经毒性的细胞类型的体外表征，并在我们实验室的体内数据进行初步研究表明，基底神经节功能障碍，尤其是NIGRO - 纹状体途径，是ADC中神经学表现不可或缺的。神经营养因子是天然存在的蛋白质，这对于ADC中影响的神经元群体的维持至关重要。提出的实验将检查以下假设：GP 120导致基底神经节的细胞死亡，而神经营养因素可以预防GP 120介导的细胞死亡。这种神经保护反过来可能会限制与大脑中HIV感染有关的神经系统并发症。