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：
8701265
负责人：
NAZIRA EL-HAGE
金额：
$ 11.33万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
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 2014-08-09
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8701265
关键词：
AIDS Dementia Complex AIDS neuropathy Autophagocytosis Autophagosome Autopsy Award Biology Brain Breeding C57BL/6 Mouse CCR5 gene CXCR4 gene Cell physiology Cells Coculture Techniques Cognitive Complex Data Dementia Disease Encephalitis Exposure to Functional disorder Goals HIV HIV-1 Highly Active Antiretroviral Therapy Homeostasis Human Image Implant Individual Infection Lead Leadership Life Lysosomes Microglia Minor Modeling Morphine Motivation Mus Nerve Degeneration Neurocognitive Neuroglia Neurons Neuropathogenesis Opiates Opioid Organelles Pathogenesis Pathology Pathway interactions Persons Placebo Control Play Population Process Proteins Research Role Running Sampling Scientist Signal Pathway Signal Transduction Staging Substance abuse problem Symptoms System Time Tissues Transfection Transgenic Mice Viral digital imaging drug of abuse gain of function genetic inducer inhibitor/antagonist insight loss of function mind control motor disorder neurodegenerative dementia neuron loss neurotropic novel programs protein aggregate public health relevance response

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感染个体发展出与HIV-1相关的神经认知障碍（手）。症状范围从较小的困难到严重的神经退行性痴呆症，即使是高度活跃的抗逆转录病毒疗法（HAART）的出现，而严重的HIV相关痴呆症也不常见，较小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，有关滥用药物对神经胶质细胞功能的作用的信息非常有限，尽管它们对于阿片反应至关重要。此外，尚不清楚滥用药物的作用以及药物滥用对神经元功能的影响。拟议的项目将研究自噬在滥用药物的情况下自噬在小胶质细胞引起的神经助剂中的作用。三个相关的特定目的针对：1）确定小胶质细胞生物学中的新机制调节HIV-1复制，以及是否通过这种途径〜2）在细胞水平上表征HIV-1的途径对HIV-1感染收敛，HIV-1在HIV的后果中诱导的溶酶体功能障碍和/或平均滥用效果是否有意义。小胶质细胞和神经元中HIV-1和吗啡激活的自噬过程的（保护性与毒性）。 El-Hage博士拥有成功的研究计划所必需的专业知识，领导和动力，获得该奖项的目的是使El-Hage博士成为一名独立的科学家。