Effects of HSV-1 reactivation from latency on aspects of neural precursor cells neurogenesis and accumulation of Alzheimer's molecular hallmarks
HSV-1从潜伏期重新激活对神经前体细胞神经发生和阿尔茨海默病分子标志积累的影响
基本信息
- 批准号:10710940
- 负责人:
- 金额:$ 36.16万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAccelerationAddressAffectAlzheimer&aposs DiseaseAmyloid beta-42Amyloid beta-ProteinAttenuatedAutopsyBiologyBrainCell Culture TechniquesCell DeathCell Differentiation processCell SeparationCellsCentral Nervous SystemClinicalCognitionDNADataDefectDementiaDevelopmentDiseaseEventExhibitsFluorescent in Situ HybridizationFunctional disorderGenerationsHealthHerpes Simplex InfectionsHerpesvirus 1HippocampusImmunohistochemistryImpaired cognitionImpairmentIn VitroInfectionLesionLinkModelingMolecularMolecular DiseaseMusNerve DegenerationNeurodegenerative DisordersNeurofibrillary TanglesNeuronal DifferentiationNeuronsOutcomePathogenesisPathologyPeptidesPhasePlayPositron-Emission TomographyPrevention therapyProductionProliferatingProphylactic treatmentProteinsRNAReportingRisk FactorsRoleSenile PlaquesSiteSymptomsSynapsesTransgenic MiceTropismViralVirusabeta accumulationadult neurogenesisaging populationamyloid peptidebrain tissueexperimental studyextracellularfamilial Alzheimer diseasehuman modelhyperphosphorylated tauimaging studyin vivoin vivo Modelinduced pluripotent stem cellinnovationmigrationmouse modelmutantnerve stem cellneuralneurogenesisneuroinflammationneuropathologynew therapeutic targetpathogenpathogenic viruspre-clinicalreactivation from latencystem cell proliferationtau Proteinstau-1
项目摘要
7. ABSTRACT
Alzheimer's disease (AD) is the leading neurodegenerative cause of dementia. Primary neuropathological
lesions of AD are extracellular plaques of fibrillized β-amyloid (Aβ) peptides and intracellular neurofibrillary
tangles of hyper-phosphorylated tau (p-tau) protein. The impairment of adult neurogenesis is an early event
in the development of AD. A recent hypothesis (“pathogen hypothesis”) proposes that herpes simplex virus
1 (HSV-1) plays a relevant role in the onset of AD. A consequence of HSV-1 reactivation in murine central
nervous system (CNS) is cognition deficits caused by impaired NPCs neurogenesis in the hippocampus.
HSV-1 infection results in Aβ42 accumulation in the NPCs in the hippocampus and these mice demonstrate
impaired neurogenesis linked to amyloid-β protein accumulation.
In the present proposal, we aim to specifically investigate the consequences of HSV-1 reactivation on
neuronal differentiation of NPCs and the generation of AD molecular hallmarks in cells undergoing viral
reactivation. We propose the following Supplemental Aims: 1) Analysis of the effects of HSV-1 reactivation
on aspects of neurogenesis, such as NPCs proliferation and differentiation; 2) Analysis of accumulation of
Aβ peptides and hyperphosphorylation of tau in NPCs during HSV-1 reactivation by combined Fluorescent
in Situ Hybridization and Immunohistochemistry (FISH-IHC).
Supplemental Aim 1 is relevant to AD because in vivo studies suggest that neurogenesis is impaired during
early stages of Alzheimer's disease and may underlie, at least in part, cognition deficit. Although abnormal
NPCs neurogenesis and cognitive decline have been described in a mouse model of HSV-1 reactivation, it
is not known whether these outcomes can be attributed to viral reactivation in NPCs.
Supplemental Aim 2 is relevant to AD because NPCs isolated from a murine model of familiar Alzheimer’s
disease exhibit hyperphosphorylation of tau. The results from this in vivo model indicate that: i) tau
hyperphosphorylation is the main contributor to impaired neurogenesis; ii) Aβ levels do not seem to be the
primary factor in the alteration of NPCs neurogenesis. However, a recent study indicates that Aβ
accumulation in NPCs is the major contributor to impaired neurogenesis in a murine model of HSV-1
reactivation. Nevertheless, it is important to note that in this study the tau hyperphosphorylation in
NSCs/NPCs had not been investigated. We propose to investigate whether altered levels of Aβ or
hyperphosphorylated tau follows HSV-1 reactivation and whether the increased levels of one of these AD
molecular hallmarks may occur in NPCs undergoing to HSV-1 reactivation.
7. 摘要
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Insights into bioinformatic approaches for repurposing compounds as anti-viral drugs.
- DOI:10.1177/20402066211036822
- 发表时间:2021-01
- 期刊:
- 影响因子:0
- 作者:Zheng W;D'Aiuto L;Demers MJ;Muralidaran V;Wood JA;Wesesky M;Chattopadhyay A;Nimgaonkar VL
- 通讯作者:Nimgaonkar VL
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David C. Bloom其他文献
Phosphorylated-tau associates with HSV-1 chromatin and correlates with nuclear speckles decondensation in low-density host chromatin regions
磷酸化tau 与单纯疱疹病毒 1 染色质相关联,并与低密度宿主染色质区域的核斑点解凝聚相关。
- DOI:
10.1016/j.nbd.2025.106804 - 发表时间:
2025-03-01 - 期刊:
- 影响因子:5.600
- 作者:
Leonardo D'Aiuto;Jill K. Caldwell;Terri G. Edwards;Chaoming Zhou;Matthew L. McDonald;Roberto Di Maio;Wood A. Joel;Vanesa R. Hyde;Callen T. Wallace;Simon C. Watkins;Maribeth A. Wesesky;Or A. Shemesh;Vishwajit L. Nimgaonkar;David C. Bloom - 通讯作者:
David C. Bloom
Herpes simplex virus-1 and varicella-zoster virus latency in ganglia
- DOI:
10.1080/13550280390194000 - 发表时间:
2003-03-01 - 期刊:
- 影响因子:1.900
- 作者:
Bradley M. Mitchell;David C. Bloom;Randall J. Cohrs;Donald H. Gilden;Peter G. E. Kennedy - 通讯作者:
Peter G. E. Kennedy
801. RNA Gene Therapy Targeting Herpes Simplex Virus
- DOI:
10.1016/j.ymthe.2006.08.890 - 发表时间:
2006-01-01 - 期刊:
- 影响因子:
- 作者:
Jia Liu;Sonal S. Tuli;David C. Bloom;Gregory S. Schultz;Steve C. Ghivizzani;Alfred S. Lewin - 通讯作者:
Alfred S. Lewin
Posterior ankyloglossia: A case report
- DOI:
10.1016/j.ijporl.2009.02.011 - 发表时间:
2009-06-01 - 期刊:
- 影响因子:
- 作者:
Michael W. Chu;David C. Bloom - 通讯作者:
David C. Bloom
David C. Bloom的其他文献
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{{ truncateString('David C. Bloom', 18)}}的其他基金
Effects of HSV-1 infection on neural progenitor cell biology in vitro and in vivo
HSV-1感染对神经祖细胞体外和体内生物学的影响
- 批准号:
10201788 - 财政年份:2020
- 资助金额:
$ 36.16万 - 项目类别:
Effects of HSV-1 infection on neural progenitor cell biology in vitro and in vivo
HSV-1感染对神经祖细胞体外和体内生物学的影响
- 批准号:
10623148 - 财政年份:2020
- 资助金额:
$ 36.16万 - 项目类别:
Effects of HSV-1 infection on neural progenitor cell biology in vitro and in vivo
HSV-1感染对神经祖细胞体外和体内生物学的影响
- 批准号:
10047416 - 财政年份:2020
- 资助金额:
$ 36.16万 - 项目类别:
Effects of HSV-1 infection on neural progenitor cell biology in vitro and in vivo
HSV-1感染对神经祖细胞体外和体内生物学的影响
- 批准号:
10395571 - 财政年份:2020
- 资助金额:
$ 36.16万 - 项目类别:
Function of histone chaperones in HSV-1 chromatin sturcture during latency, establishing maintenance and reactivation
潜伏期 HSV-1 染色质结构中组蛋白伴侣的功能、建立维持和重新激活
- 批准号:
8930277 - 财政年份:2015
- 资助金额:
$ 36.16万 - 项目类别:
Regulation of lytic and latent infection by HSV-1 encoded miRNAs
HSV-1 编码的 miRNA 对裂解和潜伏感染的调节
- 批准号:
8219674 - 财政年份:2012
- 资助金额:
$ 36.16万 - 项目类别:
Regulation of lytic and latent infection by HSV-1 encoded miRNAs
HSV-1 编码的 miRNA 对裂解和潜伏感染的调节
- 批准号:
8414420 - 财政年份:2012
- 资助金额:
$ 36.16万 - 项目类别:
Regulation of lytic and latent infection by HSV-1 encoded miRNAs
HSV-1 编码的 miRNA 对裂解和潜伏感染的调节
- 批准号:
8602830 - 财政年份:2012
- 资助金额:
$ 36.16万 - 项目类别:
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