Pathogenic mechanisms of HIV-associated pain
HIV相关疼痛的发病机制
基本信息
- 批准号:9768586
- 负责人:
- 金额:$ 57.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-09-01 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS/HIV problemAbbreviationsAcquired Immunodeficiency SyndromeAstrocytesAutopsyBackBehavioralBiopsyCommunicationDataDevelopmentDiseaseEnterobacteria phage P1 Cre recombinaseFeedbackFundingGlial Fibrillary Acidic ProteinGlycoproteinsHIVHIV Envelope Protein gp120HIV therapyHIV-1HIV-associated neurocognitive disorderHealthcareImpairmentIntrathecal InjectionsKnock-outKnockout MiceLDL-Receptor Related ProteinsLigandsMediatingMonitorMosaicismMultivesicular BodyNeuronsPainPain managementPathogenesisPathogenicityPathologicPathologyPathway interactionsPatientsPharmacologyPlayProcessQuality of lifeRoleSignal TransductionSignaling ProteinSphingomyelinaseSpinalSpinal CordTestingTreatment CostUp-RegulationWNT Signaling PathwayWnt proteinsWorkantiretroviral therapybasecentral sensitizationchronic paincostdesigndorsal horneffective therapyexosomefeedingin vivoinhibitor/antagonistinsightinterdisciplinary approachmouse modelnervous system disorderneuroAIDSnovelnovel therapeuticspain processingpatch clampreceptor
项目摘要
PROJECT SUMMARY
Pain is the most common and most costly neurological disorder in HIV-1/AIDS patients, yet current pain
treatment provides only symptomatic management that is often ineffective. Lack of deep, mechanistic
understanding of the underlying mechanism of HIV-associated pain has significantly impeded the development
of needed effective, rationale-based approaches for pain control in HIV patients. Emerging evidence suggests
a crucial role for neuron-astrocyte interactions in the spinal dorsal horn (SDH; the pain processing center in the
spinal cord) in the pathogenesis of HIV-associated pain. However, the mechanism that mediates these
intercellular interactions is largely unknown. Our work prior and preliminary studies suggest that gp120 elicits
exosome-based signals to mediate bidirectional neuron-astrocyte communication in the SDH. Importantly, the
exosome pathway is up-regulated in the SDH of the HIV patients with pathological pain. Pharmacological
inhibition of exosome secretion in the SDH blocks the expression of gp120-induced pain. We propose that
exosome-mediated neuron-astrocyte interactions play a critical role in gp120-induced pain pathogenesis.
Specifically, we hypothesize that gp120 stimulates exosome-based secretion of Wnt signaling protein from
SDH neurons, which then stimulates astrocytes to release exosomes that in return feedback to SDH pain
processing neurons to promote central sensitization. We will use an interdisciplinary approach of conditional
knockout, mosaic analysis, patch clamp recording and behavioral analysis to test this hypothesis. The
mechanistic insights gained from this project will facilitate the development of novel therapies for HIV-
associated pain targeting this underlying exosome-mediated pathogenic process.
项目摘要
疼痛是HIV-1/AIDS患者中最常见和最昂贵的神经系统疾病,
治疗仅提供通常无效的症状管理。缺乏深刻的、机械的
对HIV相关疼痛的潜在机制的理解显著阻碍了
需要有效的,合理的方法来控制艾滋病患者的疼痛。新出现的证据表明
脊髓背角(SDH;疼痛处理中心)中神经元-星形胶质细胞相互作用的关键作用,
脊髓)在HIV相关疼痛的发病机制中的作用。然而,介导这些的机制
细胞间的相互作用在很大程度上是未知的。我们的前期工作和初步研究表明,gp 120基因的表达可能是一个重要的调控因子。
外泌体信号介导SDH中的双向神经元-星形胶质细胞通讯。重要的是
外泌体通路在病理性疼痛的HIV患者的SDH中上调。药理
SDH中外来体分泌的抑制阻断了gp 120诱导的疼痛的表达。我们建议
外泌体介导的神经元-星形胶质细胞相互作用在GP 120诱导的疼痛发病机制中起关键作用。
具体地说,我们假设gp 120刺激Wnt信号蛋白的基于外泌体的分泌,
SDH神经元,然后刺激星形胶质细胞释放外泌体,以反馈SDH疼痛
处理神经元以促进中枢敏感化。我们将使用跨学科的方法,
敲除、嵌合体分析、膜片钳记录和行为分析来验证这一假设。的
从该项目中获得的机制见解将促进艾滋病毒新疗法的开发,
靶向这种潜在的外泌体介导的致病过程的相关疼痛。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
SHAO-JUN TANG其他文献
SHAO-JUN TANG的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('SHAO-JUN TANG', 18)}}的其他基金
Cellular and circuitry mechanisms of NRTI-induced pain pathogenesis in the context of opioids and HIV
阿片类药物和 HIV 背景下 NRTI 诱导的疼痛发病机制的细胞和电路机制
- 批准号:
10559782 - 财政年份:2022
- 资助金额:
$ 57.76万 - 项目类别:
Cellular and circuitry mechanisms of NRTI-induced pain pathogenesis in the context of opioids and HIV
阿片类药物和 HIV 背景下 NRTI 诱导的疼痛发病机制的细胞和电路机制
- 批准号:
10704142 - 财政年份:2022
- 资助金额:
$ 57.76万 - 项目类别:
Antiretroviral Therapy and Neuroinflammation in the CNS
抗逆转录病毒治疗和中枢神经系统神经炎症
- 批准号:
9357679 - 财政年份:2016
- 资助金额:
$ 57.76万 - 项目类别:
Antiretroviral Therapy and Neuroinflammation in the CNS
抗逆转录病毒治疗和中枢神经系统神经炎症
- 批准号:
9271670 - 财政年份:2016
- 资助金额:
$ 57.76万 - 项目类别:
Interplay of HIV-1 gp120 and opioids in astrocyte activation
HIV-1 gp120 和阿片类药物在星形胶质细胞激活中的相互作用
- 批准号:
8584926 - 财政年份:2013
- 资助金额:
$ 57.76万 - 项目类别:
Interplay of HIV-1 gp120 and opioids in astrocyte activation
HIV-1 gp120 和阿片类药物在星形胶质细胞激活中的相互作用
- 批准号:
8719076 - 财政年份:2013
- 资助金额:
$ 57.76万 - 项目类别:
Interplay of HIV-1 gp120 and opioids in astrocyte activation
HIV-1 gp120 和阿片类药物在星形胶质细胞激活中的相互作用
- 批准号:
9084524 - 财政年份:2013
- 资助金额:
$ 57.76万 - 项目类别:
Interplay of HIV-1 gp120 and opioids in astrocyte activation
HIV-1 gp120 和阿片类药物在星形胶质细胞激活中的相互作用
- 批准号:
8840924 - 财政年份:2013
- 资助金额:
$ 57.76万 - 项目类别:
Interplay of HIV-1 gp120 and opioids in astrocyte activation
HIV-1 gp120 和阿片类药物在星形胶质细胞激活中的相互作用
- 批准号:
9265050 - 财政年份:2013
- 资助金额:
$ 57.76万 - 项目类别:
Wnt signaling in glial activation during HIV-associated chronic pain pathogenesis
HIV相关慢性疼痛发病机制中神经胶质激活中的Wnt信号传导
- 批准号:
8846150 - 财政年份:2012
- 资助金额:
$ 57.76万 - 项目类别:
相似海外基金
Real-time Disambiguation of Abbreviations in Clinical Notes
临床记录中缩写词的实时消歧
- 批准号:
8077875 - 财政年份:2010
- 资助金额:
$ 57.76万 - 项目类别:
Real-time Disambiguation of Abbreviations in Clinical Notes
临床记录中缩写词的实时消歧
- 批准号:
7866149 - 财政年份:2010
- 资助金额:
$ 57.76万 - 项目类别:
Real-time Disambiguation of Abbreviations in Clinical Notes
临床记录中缩写词的实时消歧
- 批准号:
8589822 - 财政年份:2010
- 资助金额:
$ 57.76万 - 项目类别:
Real-time Disambiguation of Abbreviations in Clinical Notes
临床记录中缩写词的实时消歧
- 批准号:
8305149 - 财政年份:2010
- 资助金额:
$ 57.76万 - 项目类别: