Identification and evaluation of novel therapeutic targets for virus-induced neuronal disease
病毒引起的神经元疾病新治疗靶点的鉴定和评估
基本信息
- 批准号:8867128
- 负责人:
- 金额:$ 46.61万
- 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:2012-06-01 至 2017-05-31
- 项目状态:已结题
- 来源:
- 关键词:AcyclovirAnimalsArbovirusesBiological AssayBrainBrain DiseasesCell DeathCentral Nervous System DiseasesCessation of lifeDataDidelphidaeDiseaseDisease OutcomeEncephalitisEncephalitis VirusesEquus caballusEvaluationFamilyGene DeletionGene ExpressionGene TargetingGenesGeneticGenomic approachGoalsHerpes encephalitisHospitalizationHumanIndividualInfectionJapanese encephalitis virusMethodsMicroarray AnalysisModelingMorbidity - disease rateMusNeuronsPathogenesisPathway AnalysisPathway interactionsPatternPhaseRNARNA InterferenceRegulationReovirusRoleSignal PathwaySignal TransductionSignaling MoleculeSignaling Pathway GeneSmall Interfering RNASourceSystemTreatment EfficacyViralViral EncephalitisViral PathogenesisVirusVirus DiseasesWest Nile viruscell growth regulationdifferential expressiondisabilityeffective therapyhuman diseaseimprovedin vivoinhibitor/antagonistinnovationmortalityneurotropicnew therapeutic targetnovelnovel strategiesprotein expressionresearch studytherapeutic evaluationtherapeutic targettranscription factortreatment strategy
项目摘要
Viral encephalitis, including encephalitis induced by the arboviruses West Nile virus (WNV) and
Japanese encephalitis virus (JEV), is a major source of morbidity and mortality both in the U.S. and throughout
the world. Proven treatments for viral encephalitis are limited to only a few viruses and even when treatments
exist (e.g. acyclovir for herpes simplex encephalitis) disability and death remain significant. There are currently
no effective treatments for arbovirus-induced encephalitis. Novel and broadly applicable strategies for the
treatment of neurotropic viral infections are desperately needed.
We will perform microarray analysis on RNA extracted from the brains of mice infected with WNV or
JEV in order to identify novel cellular genes and pathways that are differentially regulated in the brain following
virus infection and which may provide therapeutic targets for viral encephalitis. Genes and pathways that are
differentially regulated in the brains of mice infected with both viruses will be preferentially used as identified
targets. We then propose to perform an inventive PCR approach using pairs of neurovirulent and
neuroattenuated viral strains, different treatment conditions and additional encephalitis viruses to identify
pathogenic genes and signaling pathways which have the highest likelihood of providing therapeutic targets for
viral encephalitis. In the final part of this proposal we will evaluate these targets in in vivo and ex vivo models of
viral pathogenesis using genetic, pharmacologic and siRNA directed approaches.
It is expected that these studies will identify and evaluate novel therapeutic targets for virus
encephalitis. Although the main goal of the proposal to identify novel therapeutic targets for WNV and JEV the
inclusion of additional encephalitic viruses may identify broad spectrum therapeutic targets for encephalitis
induced by a wide variety of different viruses. Our studies may also have relevance for other diseases of the
central nervous system.
病毒性脑炎,包括由虫媒病毒西尼罗河病毒(WNV)和
日本脑炎病毒 (JEV) 是美国乃至全世界发病率和死亡率的主要来源
世界。经证实的病毒性脑炎治疗方法仅限于少数病毒,甚至当治疗
存在(例如阿昔洛韦治疗单纯疱疹脑炎)残疾和死亡仍然很严重。目前有
对于虫媒病毒引起的脑炎没有有效的治疗方法。新颖且广泛适用的策略
迫切需要治疗嗜神经病毒感染。
我们将对从感染西尼罗河病毒或病毒的小鼠大脑中提取的 RNA 进行微阵列分析
JEV旨在识别大脑中差异调节的新细胞基因和通路
病毒感染,可能为病毒性脑炎提供治疗靶点。基因和途径
感染两种病毒的小鼠大脑中的差异调节将优先使用已确定的
目标。然后,我们建议使用成对的神经毒力和
神经减毒病毒株、不同的治疗条件和其他脑炎病毒来识别
最有可能为疾病提供治疗靶点的致病基因和信号通路
病毒性脑炎。在本提案的最后部分,我们将在体内和离体模型中评估这些目标
使用遗传、药理学和 siRNA 指导方法研究病毒发病机制。
预计这些研究将确定和评估病毒的新治疗靶点
脑炎。尽管该提案的主要目标是确定西尼罗河病毒和乙脑病毒的新治疗靶点,
纳入其他脑炎病毒可能会确定脑炎的广谱治疗靶点
由多种不同病毒引起。我们的研究也可能与其他疾病有关
中枢神经系统。
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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Kenneth L. Tyler其他文献
EV68-228-N monoclonal antibody treatment halts progression of paralysis in a mouse model of EV-D68 induced acute flaccid myelitis
EV68-228-N 单克隆抗体治疗可阻止 EV-D68 诱导的急性弛缓性脊髓炎小鼠模型中瘫痪的进展
- DOI:
10.1128/mbio.03906-24 - 发表时间:
2025-02-25 - 期刊:
- 影响因子:4.700
- 作者:
Michael J. Rudy;Courtney J. Wilson;Brendan Hinckley;Danielle C. Baker;Joshua M. Royal;Marshall P. Hoke;Miles B. Brennan;Matthew R. Vogt;Penny Clarke;Kenneth L. Tyler - 通讯作者:
Kenneth L. Tyler
Cerebral amyloid angiopathy with multiple intracerebral hemorrhages. Case report.
脑淀粉样血管病伴多发性脑出血。
- DOI:
10.3171/jns.1982.57.2.0286 - 发表时间:
1982 - 期刊:
- 影响因子:4.1
- 作者:
Kenneth L. Tyler;Charles E. Poletti;R. Heros - 通讯作者:
R. Heros
A rationally designed 2C inhibitor prevents enterovirus D68-infected mice from developing paralysis
合理设计的 2C 抑制剂可防止肠道病毒 D68 感染的小鼠出现瘫痪
- DOI:
10.1038/s41467-025-61083-8 - 发表时间:
2025-07-01 - 期刊:
- 影响因子:15.700
- 作者:
Kan Li;Michael J. Rudy;Yanmei Hu;Haozhou Tan;George Lambrinidis;Xiangmeng Wu;Kyriakos Georgiou;Bin Tan;Joshua Frost;Courtney Wilson;Penny Clarke;Antonios Kolocouris;Qing-yu Zhang;Kenneth L. Tyler;Jun Wang - 通讯作者:
Jun Wang
Case 45-1988
案例45-1988
- DOI:
10.1056/nejm198811103191908 - 发表时间:
1988 - 期刊:
- 影响因子:0
- 作者:
Kenneth L. Tyler;E. T. Hedley - 通讯作者:
E. T. Hedley
Usutu virus disease: a potential problem for North America?
乌苏图病毒病:北美潜在的问题?
- DOI:
10.1007/s13365-019-00818-y - 发表时间:
2019-12-19 - 期刊:
- 影响因子:1.900
- 作者:
Christine M. Gill;Ronak K. Kapadia;J. David Beckham;Amanda L. Piquet;Kenneth L. Tyler;Daniel M. Pastula - 通讯作者:
Daniel M. Pastula
Kenneth L. Tyler的其他文献
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{{ truncateString('Kenneth L. Tyler', 18)}}的其他基金
Genomic and molecular determinants of EV-D68 neuroinvasive disease
EV-D68神经侵袭性疾病的基因组和分子决定因素
- 批准号:
10657198 - 财政年份:2023
- 资助金额:
$ 46.61万 - 项目类别:
EV-D68-induced CNS disease: pathogenic mechanisms and identification of therapeutic targets.
EV-D68诱导的中枢神经系统疾病:致病机制和治疗靶点的鉴定。
- 批准号:
10225583 - 财政年份:2018
- 资助金额:
$ 46.61万 - 项目类别:
EV-D68-induced CNS disease: pathogenic mechanisms and identification of therapeutic targets.
EV-D68诱导的中枢神经系统疾病:致病机制和治疗靶点的鉴定。
- 批准号:
9769165 - 财政年份:2018
- 资助金额:
$ 46.61万 - 项目类别:
EV-D68-induced CNS disease: pathogenic mechanisms and identification of therapeutic targets.
EV-D68诱导的中枢神经系统疾病:致病机制和治疗靶点的鉴定。
- 批准号:
9436831 - 财政年份:2017
- 资助金额:
$ 46.61万 - 项目类别:
Identification and evaluation of novel therapeutic targets for virus-induced neuronal disease
病毒引起的神经元疾病新治疗靶点的鉴定和评估
- 批准号:
8354615 - 财政年份:2012
- 资助金额:
$ 46.61万 - 项目类别:
Identification and evaluation of novel therapeutic targets for virus-induced neuronal disease
病毒引起的神经元疾病新治疗靶点的鉴定和评估
- 批准号:
8841447 - 财政年份:2012
- 资助金额:
$ 46.61万 - 项目类别:
Identification and evaluation of novel therapeutic targets for virus-induced neuronal disease
病毒引起的神经元疾病新治疗靶点的鉴定和评估
- 批准号:
8471054 - 财政年份:2012
- 资助金额:
$ 46.61万 - 项目类别:
Mechanisms of virus-induced injury in the brain and spinal cord
病毒引起的脑和脊髓损伤的机制
- 批准号:
8598010 - 财政年份:2011
- 资助金额:
$ 46.61万 - 项目类别:
Cellular genes and signaling pathways as therapeutic targets for virus-induced CN
细胞基因和信号通路作为病毒诱导 CN 的治疗靶点
- 批准号:
8215547 - 财政年份:2011
- 资助金额:
$ 46.61万 - 项目类别:
Role of Microglia in Protection Against West Nile Virus-induced CNS Injury: mechanisms and treatment strategies
小胶质细胞在预防西尼罗河病毒引起的中枢神经系统损伤中的作用:机制和治疗策略
- 批准号:
10513299 - 财政年份:2011
- 资助金额:
$ 46.61万 - 项目类别:
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