Molecular Segregation of Parkinson’s Disease by Patient-Derived Neurons
患者来源的神经元对帕金森病的分子分离
基本信息
- 批准号:10613419
- 负责人:
- 金额:$ 44.9万
- 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:2020-06-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAgeBackBiological MarkersBradykinesiaCategoriesCellsClinicalClinical Trials DesignComplexDevelopmentDiagnosisDiagnosticDiseaseDopamineFibroblastsGene ExpressionGene Expression ProfileGenesGeneticGoalsHumanIdiopathic Parkinson DiseaseInduced pluripotent stem cell derived neuronsLaboratoriesMethodsMidbrain structureMolecularMolecular ProfilingNeuronal DifferentiationNeuronsOnset of illnessOxidative StressParkinson DiseasePatientsPhysiologyPreparationPrognosisPropertyResearchRest TremorSamplingSeriesShapesSkinStem Cell DevelopmentSymptomsTestingTissue-Specific Gene ExpressionTremorUrinary tractbiomarker developmentcohortdisease diagnosisdisorder subtypedopaminergic neuronendophenotypeimprovedinduced pluripotent stem cellinnovationinnovative technologiesinsightnew technologynovelposture instabilitypredictive markerresearch and developmentsegregationsexstemstem cell technologytherapeutic developmenturinary
项目摘要
Parkinson’s disease (PD) is defined by its hallmark locomotor symptoms including tremor, rigidity,
bradykinesia and postural instability, which are caused by a progressive loss of nigral dopaminergic (DA)
neurons. A well-recognized categorization of Parkinson’s disease is based on whether rest tremor is present or
not at disease onset. PD patients who have rest tremor at onset generally have slower progression and better
prognosis than PD patients without rest tremor at onset. Our preliminary study showed that the expression of
genes controlling dopamine synthesis, sequestration and degradation was significantly different between
midbrain DA neurons derived from induced pluripotent stem cells (iPSC) of normal subjects vs. idiopathic PD
patients. Expression of some of these genes was also significantly different between idiopathic PD patients
with or without rest tremor at onset. We have developed a series of new technologies including the
differentiation of iPSCs to A9 DA neurons and the direct conversion of human skin fibroblasts and urinary track
cells (UTCs) to midbrain DA neurons. Using these innovative technologies, the proposal aims to identify
molecular signatures that can segregate PD patients and normal subjects, and distinguish PD patients with or
without rest tremor at onset. The converging development of stem cell technologies enables this project to
identify molecular signatures of idiopathic Parkinson’s disease, which will significantly advance PD diagnosis,
research and therapeutic development.
帕金森氏病(PD)由其标志性运动症状定义,包括震颤、僵硬,
运动迟缓和姿势不稳定,这是由黑质多巴胺能(DA)的进行性丧失引起的
神经元帕金森病的一个公认的分类是基于是否存在静息震颤或
而不是在发病时。发作时有静止性震颤的PD患者通常进展较慢,
PD患者发病时无静息震颤。我们的初步研究表明,
控制多巴胺合成、螯合和降解的基因在
源自正常受试者与特发性PD的诱导多能干细胞(iPSC)的中脑DA神经元
患者其中一些基因的表达在特发性PD患者之间也有显著差异
发作时伴有或不伴有静止性震颤。我们开发了一系列新技术,包括
iPSC向A9 DA神经元的分化以及人皮肤成纤维细胞和尿道的直接转化
细胞(UTCs)到中脑DA神经元。利用这些创新技术,该提案旨在确定
可以分离PD患者和正常受试者的分子特征,并区分PD患者或
发作时无静息震颤。干细胞技术的融合发展使该项目能够
识别特发性帕金森病的分子特征,这将显著推进PD诊断,
研究和治疗开发。
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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JIAN FENG其他文献
JIAN FENG的其他文献
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{{ truncateString('JIAN FENG', 18)}}的其他基金
Epigenetics-Based Autism Treatment with Animal Models and Human Stem Cells
利用动物模型和人类干细胞进行基于表观遗传学的自闭症治疗
- 批准号:
10651463 - 财政年份:2023
- 资助金额:
$ 44.9万 - 项目类别:
Administrative Supplement to Molecular Segregation of Parkinson’s Disease by Patient-derived Neurons
患者来源神经元对帕金森病分子分离的行政补充
- 批准号:
10709193 - 财政年份:2023
- 资助金额:
$ 44.9万 - 项目类别:
Transcriptomic and Circuitry Aberrations in Alzheimer’s Disease
阿尔茨海默氏病的转录组和电路畸变
- 批准号:
10556747 - 财政年份:2022
- 资助金额:
$ 44.9万 - 项目类别:
Molecular Segregation of Parkinson’s Disease by Patient-derived Neurons
患者来源的神经元对帕金森病的分子分离
- 批准号:
10379969 - 财政年份:2020
- 资助金额:
$ 44.9万 - 项目类别:
Molecular Segregation of Parkinson’s Disease by Patient-derived Neurons
患者来源的神经元对帕金森病的分子分离
- 批准号:
10046128 - 财政年份:2020
- 资助金额:
$ 44.9万 - 项目类别:
Molecular Segregation of Parkinson’s Disease by Patient-derived Neurons
患者来源的神经元对帕金森病的分子分离
- 批准号:
10175070 - 财政年份:2020
- 资助金额:
$ 44.9万 - 项目类别:
The Interaction of parkin and environmental toxins in Parkinson’s disease
帕金森病中帕金蛋白与环境毒素的相互作用
- 批准号:
9898312 - 财政年份:2018
- 资助金额:
$ 44.9万 - 项目类别:
The Interaction of parkin and environmental toxins in Parkinson’s disease
帕金森病中帕金蛋白与环境毒素的相互作用
- 批准号:
10215394 - 财政年份:2018
- 资助金额:
$ 44.9万 - 项目类别:
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