Oxidative Stress Markers and HIV Dementia

氧化应激标志物和艾滋病毒痴呆

基本信息

批准号：
7596882
负责人：
NED C SACKTOR
金额：
$ 36.4万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-08 至 2011-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7596882
关键词：
4 hydroxynonenal AIDS Dementia Complex Acids Age Aldehydes Anti-Retroviral Agents Antioxidants Astrocytes Attenuated Biological Assay Brain Cell Death Ceramides Clinical Controlled Clinical Trials Data Dementia Development Equilibrium Failure Functional disorder HIV HIV Infections Highly Active Antiretroviral Therapy Immune Immunologic Markers Impaired cognition Impairment Incidence Individual Infection Inflammation Inflammatory Injury Laboratory Markers Magnetic Resonance Spectroscopy Measures Membrane Membrane Lipids Membrane Potentials Minocycline Mitochondria Modeling Nervous System Trauma Neuraxis Neurocognitive Neuronal Injury Neuropsychological Tests New Agents Oxidation-Reduction Oxidative Stress Pathogenesis Patients Performance Phospholipids Play Polyunsaturated Fatty Acids Process Production Prospective Studies Proteins Reactive Oxygen Species Research Personnel Risk Role SIV Severities Site Sphingomyelins Staging Stress Surrogate Markers Syndrome Testing Therapeutic Toxin United States antioxidant therapy burnout cellular targeting chemokine cohort cytokine improved indium arsenide inflammatory marker innovation macrophage mortality neuroimaging novel novel marker oxidation programs protein function research study therapeutic target young adult

项目摘要

DESCRIPTION (provided by applicant): HIV dementia (HIV-D) is one of the most common causes of dementia in young adults in the United States. Aberrant immune activation and oxidative stress within the central nervous system (CMS) play a significant role in the development of HIV-D. Disruptions in cytokine and redox balance produce reactive oxygen species which can attack proteins, deoxynucleic acids, and lipid membranes resulting in cellular dysfunction and cell death. Recent data from our group demonstrate increases in several markers of oxidative stress, specifically, ceramide, sphingomyelin, and 4-hydroxynonenal (HNE). The project will assemble a cohort of HIV+ individuals with varying degrees of neurocognitive impairment: 1) to define the association between markers of oxidative stress and HIV-D in a cohort of HAART-treated subjects and to determine the relationship between these markers and laboratory markers of macrophage and astrocyte activation and neuroimaging markers of inflammation and neuronal injury, 2) to determine whether markers of oxidative stress predict either the reversibility or the progression of HIV-D, and 3) to determine whether the antioxidant treatment, minocycline is safe in patients with HIV-D, improves HIV associated cognitive impairment, and decreases markers of oxidative stress. We propose the first large-scale prospective study to quantify novel markers of oxidative stress in individuals with HIV-associated cognitive impairment receiving HAART. This proposal examines the interrelationship between these markers and novel immune activation and neuroimaging markers of inflammation and neuronal injury to define the role of oxidative stress in the pathogenesis of HIV-D. This proposal will potentially identify new cellular targets of HIV-D treatment, and we will initiate a controlled clinical trial to test a new agent for the treatment of HIV-D. We believe that oxidative stress plays a significant role in the development of HIV-D, and strategies to decrease oxidative stress may serve as a useful therapeutic target to treat HIV-D.

描述（由申请人提供）：HIV痴呆症（HIV-D）是美国年轻人最常见的痴呆症原因之一。中枢神经系统（CMS）内的异常免疫激活和氧化应激在HIV-D的发展中起着重要作用。细胞因子和氧化还原平衡的破坏会产生活性氧，可攻击蛋白质，脱氧核酸和脂质膜，从而导致细胞功能障碍和细胞死亡。来自我们组的最新数据表明，氧化应激的几种标志物，具体是神经酰胺，鞘磷脂和4-羟基诺纳尔（HNE）。该项目将组装成不同程度的神经认知障碍的HIV+个体：1）在一系列经过HAART治疗的受试者中定义氧化应激和HIV-D标记之间的关联，并确定这些标记物与巨噬细胞和星形分析标记的这些标记和实验室标记之间的关系，并确定标记的标记，该标记是指确定的，并定义了2个自动级别的标记。氧化应激可以预测HIV-D的可逆性或进展，3）确定HIV-D患者的抗氧化剂治疗，米诺环素，改善HIV相关的认知障碍并降低氧化应激的标志物。我们提出了第一项大规模的前瞻性研究，以量化接受HAART患有HIV相关认知障碍的个体中氧化应激的新标志物。该建议研究了这些标记物与炎症和神经元损伤的新型免疫激活和神经影像学标记之间的相互关系，以定义氧化应激在HIV-D发病机理中的作用。该建议将有可能识别HIV-D治疗的新细胞靶标，我们将启动对照临床试验，以测试一种新药物治疗HIV-D。我们认为，氧化应激在HIV-D的发展中起着重要作用，减少氧化应激的策略可能是治疗HIV-D的有用治疗靶标。