Texas Repository for AIDS Neuropathogenesis Research

描述(由申请人提供)：德克萨斯州神经艾滋病研究中心(TNRC；“Texas”)的续签申请符合RFAMH-08-021。德克萨斯州是国家神经艾滋病组织联盟(NNTC)的一部分，该联盟包括在Mt.加州大学洛杉矶分校西奈医学院和加州大学圣地亚哥分校。申请的A部分对所有4个地点都是相同的，并包含NNTC的总体目标、业务和共同议程。B部分是场地特定的应用程序。德克萨斯州将讨论A部分的科学议程如下：1)在宿主遗传学方面，我们通过测试和构建基于病理的NNTC材料的DNA库来为该单位做好准备。目前正在使用556个DNA分离物进行合作，并将其作为NNTC使用的模板。2)对于神经病毒学目标，德克萨斯州的部门已经准备好合作，开发一种在尸检大脑样本中检测艾滋病毒载量的持久分析方法，该方法将用于NNTC的A部分议程。3)在德克萨斯州的生物标志物领域 将利用我们对NNTC感觉神经节的独特蛋白质组分析结果，在与NNTC合作开发周围神经病变标记物的需求方面发挥主要作用。4)德克萨斯州准备通过在NNTC驱动的R01项目中获得新的见解来合作治疗艾滋病毒神经精神共病，以阐明改变的多巴胺受体在可卡因使用和抑郁中的作用；我们将为A部分议程贡献新的数据和技术。5)德克萨斯州已经准备好在衰老共病领域进行互动；在NNTC驱动的R01中探索了一些技术，以确定干扰素反应如何导致蛋白质错误折叠和包括淀粉样蛋白在内的大脑蛋白质的病理性堆积。我们计划增加德克萨斯州队列中的老年人群，以增加对患有艾滋病毒/艾滋病的老年患者进行转化性研究的可行性。6)德克萨斯州已经准备好应对神经化学突破的发现，因为我们在NNTC基因阵列项目中发挥了关键作用。我们将寻求干扰素反应蛋白作为生物标志物，这是A部分议程的一个关键重点。7)德克萨斯州已经准备好在描绘灰质和白质病理对特定神经认知领域的个体影响的努力中发挥作用；我们为A部分议程贡献了一个有用的白质生物标记物，这为进一步发展打开了大门。8)德克萨斯州将继续在A部分议程中领导NNTC的神经病理质量保证计划。这些利基符合德克萨斯州的某些优势，如果充分利用，可以提供广度和影响到NNTC的议程。德克萨斯州随时准备再次合作，以确保NNTC在未来仍然是一项重要和持久的国家资源。 A部分：

DESCRIPTION (provided by applicant): This application for renewal of the Texas NeuroAIDS Research Center (TNRC; "Texas") responds to RFAMH-08-021. Texas is part of the National NeuroAIDS Tissue Consortium (NNTC) which includes 3 additional sites at the Mt. Sinai School of Medicine, UCLA, and the UC San Diego. Part A of the application is identical for all 4 sites and contains overall aims, operations and shared agendas of the NNTC. Part B is the Site-specific application. Texas will address the Part A scientific agenda as follows: 1) In host genetics we primed the unit by testing and constructing a pathologically based DNA bank of NNTC materials. Collaboration is underway using 556 DNA isolates, and serves as a template for utilization by the NNTC. 2) For neurovirology aims the Texas unit is primed to collaborate by developing a durable assay of HIV load in autopsy brain specimens that will be used in the NNTC Part A agenda. 3) In the area of biomarkers, Texas will play a prime role in collaborating with the NNTC's need to developing markers of peripheral neuropathy, using results from our unique proteomic analysis of NNTC sensory ganglia. 4) Texas is primed to collaborate in HIV neuropsychiatric comorbidity by expanding upon new insights obtained in an NNTC driven R01 project to elucidate the role of altered dopamine receptors in cocaine use and depression; we will contribute new data and technology to the Part A agenda. 5) Texas is primed to interact in the area of aging comorbidity; techniques were scouted in an NNTC-driven R01 to determine how interferon responses drive protein misfolding and pathological accumulation of brain protein including amyloid. We plan to increase the pool of elderly people in Texas cohort to increase the feasibility of performing translational studies in elderly people with HIV/AIDS. 6) Texas is primed to address discovery of neurochemical breakthroughs because we played a key role in the NNTC gene array project. We will pursue interferon response proteins as biomarkers, which is a key focus of the Part A agenda. 7) Texas is primed to play a part in the drive to delineate the individual effects of gray and white matter pathology on specific neurocognitive domains; we contributed a useful biomarker in white matter to the Part A agenda, which opens the door to further development. 8) Texas will continue to lead the neuropathology quality assurance program of the NNTC in the Part A agenda. These niches conform to certain strengths of Texas that, if exploited fully, can provide breadth and reach to the NNTC agenda. Texas stands ready again to work together to insure that the NNTC remains a vital and lasting national resource in the future. Part A: