Role of Autophagy in Microglia-induced NeuroAIDS in Substance Abuse
自噬在小胶质细胞诱导的药物滥用中的神经艾滋病中的作用
基本信息
- 批准号:8584593
- 负责人:
- 金额:$ 38.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-07-15 至 2018-03-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS Dementia ComplexAIDS neuropathyAutophagocytosisAutophagosomeAutopsyAwardBiologyBrainBreedingC57BL/6 MouseCCR5 geneCXCR4 geneCell physiologyCellsCoculture TechniquesCognitiveComplexDataDementiaDiseaseEncephalitisExposure toFunctional disorderGoalsHIVHIV-1Highly Active Antiretroviral TherapyHomeostasisHumanImageImplantIndividualInfectionLeadLeadershipLifeLysosomesMicrogliaMinorModelingMorphineMotivationMusNerve DegenerationNeurocognitiveNeurogliaNeuronsNeuropathogenesisOpiatesOpioidOrganellesPathogenesisPathologyPathway interactionsPersonsPlacebo ControlPlayPopulationProcessProteinsResearchRoleRunningSamplingScientistSignal PathwaySignal TransductionStagingSubstance abuse problemSymptomsSystemTimeTissuesTransfectionTransgenic MiceViraldigital imagingdrug of abusegain of functiongenetic inducerinhibitor/antagonistinsightloss of functionmind controlmotor disorderneurodegenerative dementianeuron lossneurotropicnovelprogramsprotein aggregatepublic health relevanceresponse
项目摘要
DESCRIPTION (provided by applicant): Approximately one-third of HIV-1 infected individuals develop HIV-1-associated neurocognitive disorders (HAND). Symptoms range from minor difficulties to severe neurodegenerative dementia and even with the advent of highly active antiretroviral therapy (HAART), while severe HIV-associated dementia is less common, minor cognitive motor disorders remains an important part of infection. The deleterious effects of opiates are complex and information regarding the actions of drugs of abuse on glial cell function is very limited though they are known to be critical to opiate response. Moreover, the consequent effects of the actions of drugs of abuse and the manifestation of substance abuse on neuronal function are not well known. The proposed project will investigate the role of autophagy in microglia-induced neuroAIDS in the context of substance abuse. The three correlated specific aims are directed at: 1) identifying a novel mechanism in the biology of microglia that regulates HIV-1 replication and whether morphine converges on HIV-1 infection through this pathway~ 2) characterization at cellular levels the consequences of HIV-1 induced lysosomal dysfunction and whether prior and/ or concurrent substance abuse modifies cell function~ 3) examining the signaling pathways and the significance (protective vs. toxic) of the autophagy process activated by HIV-1 and morphine in microglia cells and neurons. Dr. El-Hage has the expertise, leadership, and motivation necessary to run a successful research program and the purpose of getting this award is to enable Dr. El-Hage to become an independent scientist.
描述(由申请人提供):大约三分之一的HIV-1感染者发展为HIV-1相关的神经认知障碍(HAND)。症状范围从轻微的困难到严重的神经退行性痴呆,甚至随着高活性抗逆转录病毒疗法(HAART)的出现,虽然严重的艾滋病毒相关痴呆不太常见,但轻微的认知运动障碍仍然是感染的重要组成部分。阿片类药物的有害作用是复杂的,关于滥用药物对神经胶质细胞功能的作用的信息非常有限,尽管已知它们对阿片类药物反应至关重要。此外,药物滥用的作用和药物滥用对神经元功能的表现所产生的后果尚不清楚。拟议的项目将研究自噬在药物滥用背景下小胶质细胞诱导的神经艾滋病中的作用。这三个相关的具体目标是:1)确定调节HIV-1复制的生物学新机制,以及吗啡是否通过这一途径聚集在HIV-1感染上;2)在细胞水平上表征HIV-1诱导的溶酶体功能障碍的后果,以及先前和/或同时滥用药物是否会改变细胞功能;3)检测小胶质细胞中HIV-1和吗啡激活的自噬过程的信号通路和意义(保护性与毒性)和神经元。El-Hage博士拥有成功开展研究项目所需的专业知识、领导力和动力,获得这个奖项的目的是使El-Hage博士成为一名独立的科学家。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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NAZIRA EL-HAGE其他文献
NAZIRA EL-HAGE的其他文献
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{{ truncateString('NAZIRA EL-HAGE', 18)}}的其他基金
Function of astrocytes autophagy in brain homeostasis and opioid-induced maladaptive behavior and addiction, in the context of HIV
HIV背景下星形胶质细胞自噬在大脑稳态和阿片类药物诱导的适应不良行为和成瘾中的功能
- 批准号:
10619748 - 财政年份:2023
- 资助金额:
$ 38.13万 - 项目类别:
Develop and evaluate efficacy of nanoformulated siBeclin1 delivered intranasally to eliminate HIV in brain
开发并评估鼻内递送的纳米制剂 siBeclin1 消除大脑中 HIV 的功效
- 批准号:
9893032 - 财政年份:2019
- 资助金额:
$ 38.13万 - 项目类别:
Impact of μ-opioid receptor (MOR) splice variant interactions with the chemokine receptor CCR5 in the context of morphine and HIV-1 entry inhibitor therapy
在吗啡和 HIV-1 进入抑制剂治疗背景下,μ-阿片受体 (MOR) 剪接变异体与趋化因子受体 CCR5 相互作用的影响
- 批准号:
9308938 - 财政年份:2016
- 资助金额:
$ 38.13万 - 项目类别:
Impact of μ-opioid receptor (MOR) splice variant interactions with the chemokine receptor CCR5 in the context of morphine and HIV-1 entry inhibitor therapy
在吗啡和 HIV-1 进入抑制剂治疗背景下,μ-阿片受体 (MOR) 剪接变异体与趋化因子受体 CCR5 相互作用的影响
- 批准号:
9064917 - 财政年份:2016
- 资助金额:
$ 38.13万 - 项目类别:
Role of Autophagy in Microglia-induced NeuroAIDS in Substance Abuse
自噬在小胶质细胞诱导的药物滥用中的神经艾滋病中的作用
- 批准号:
8823758 - 财政年份:2014
- 资助金额:
$ 38.13万 - 项目类别:
Role of Autophagy in Microglia-induced NeuroAIDS in Substance Abuse
自噬在小胶质细胞诱导的药物滥用中的神经艾滋病中的作用
- 批准号:
8919084 - 财政年份:2014
- 资助金额:
$ 38.13万 - 项目类别:
Role of Autophagy in Microglia-induced NeuroAIDS in Substance Abuse
自噬在小胶质细胞诱导的药物滥用中的神经艾滋病中的作用
- 批准号:
9036365 - 财政年份:2014
- 资助金额:
$ 38.13万 - 项目类别:
Role of Autophagy in Microglia-induced NeuroAIDS in Substance Abuse
自噬在小胶质细胞诱导的药物滥用中的神经艾滋病中的作用
- 批准号:
9264742 - 财政年份:2014
- 资助金额:
$ 38.13万 - 项目类别:
Role of Autophagy in Microglia-induced NeuroAIDS in Substance Abuse
自噬在小胶质细胞诱导的药物滥用中的神经艾滋病中的作用
- 批准号:
8701265 - 财政年份:2013
- 资助金额:
$ 38.13万 - 项目类别:
Oxidative damage and proteasome activity: Role of opioid in HIV-HCV infection
氧化损伤和蛋白酶体活性:阿片类药物在 HIV-HCV 感染中的作用
- 批准号:
7777398 - 财政年份:2009
- 资助金额:
$ 38.13万 - 项目类别: