Study of Novel Brain Toxin Associated With HIV Dementia

与艾滋病毒痴呆相关的新型脑毒素的研究

• 批准号: 6895055
• 负责人: Dana Giulian
• 金额: $ 51.8万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-07 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6895055
• 关键词: AIDS dementia complex; AIDS therapy; albino rat; antiAIDS agent; biomarker; carbohydrate structure; cerebrospinal fluid; clinical research; cognition; heparan sulfate; human immunodeficiency virus 1; human subject; longitudinal human study; lumbar puncture; neuropathology; neuropsychological tests; neurotoxins; oligosaccharides; psychoneuroimmunology; tissue /cell culture

DESCRIPTION (provided by applicant): HIV-associated dementia (HAD) involves destruction of neurons and synapses. Although it is agreed that brain inflammatory cells, including brain microglia and invading blood monocytes, participate in this CNS-damaging pathway by release of neurotoxins, the underlying mechanisms to account for neuropathogenesis of HAD remain uncertain. We have recently found a novel class of neurotoxins released by HIV-infected mononuclear cells. Extensive background study shows that this neurotoxin family is found in the cerebrospinal fluid (CSF) of HIV/AIDS volunteers and is closely associated with degrees of cognitive impairment. In order to uncover fundamental immuno-pathologic mechanisms of HAD, we will explore the HIV-elicited neurotoxin by examining its structural features, its mechanisms of action, and its ability to predict cognitive decline among HIV/AIDS volunteers. Further study will consider the effect of HAART on this CSF biomarker. This work represents transformational research that will help to delineate an immune pathway common to HAD and to other forms of dementia and will contribute to the development of neuroprotective treatments, which do not yet exist.

描述（由申请人提供）：与HIV相关的痴呆（HAT）涉及神经元和突触的破坏。尽管人们同意，包括脑炎性细胞，包括脑部小胶质细胞和入侵血液核细胞，通过释放神经毒素参与了这种CNS损害途径，但考虑到神经病发生的基本机制仍然不确定。我们最近发现了一种由HIV感染的单核细胞释放的新型神经毒素。广泛的背景研究表明，这种神经毒素家族是在HIV/AIDS志愿者的脑脊液（CSF）中发现的，并且与认知障碍程度密切相关。 为了揭示HAD的基本免疫病理机制，我们将通过检查其结构特征，其作用机理以及预测HIV/AIDS志愿者认知能力下降的能力来探索艾滋病毒引起的神经毒素。进一步的研究将考虑HAART对此CSF生物标志物的影响。 这项工作代表了变革性研究，将有助于描述一种常见的人和其他形式的痴呆症的免疫途径，并将有助于神经保护治疗的发展，而神经保护疗法尚未存在。