Closing the gap between structural biology and translational science for amyloid
缩小淀粉样蛋白结构生物学和转化科学之间的差距
基本信息
- 批准号:10630761
- 负责人:
- 金额:$ 6.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AmyloidAmyloid FibrilsAmyloid beta-ProteinAmyloidosisBinding ProteinsBiologyCellsClinicCoculture TechniquesCryoelectron MicroscopyDepositionDetectionDevelopmentDiagnosisDiagnosticDiseaseDisease modelEnsureEtiologyLaboratoriesMapsMicrotubulesMusNamesPathologicPatientsPeptidesPolymorphPrealbuminPrognosisProteinsResolutionRoleSamplingStructureSystemTauopathiesTherapeuticTranslational Researchalpha synucleinamyloid pathologydesignhigh riskmultidisciplinaryprogramsprotein TDP-43structural biologysymptomatologytau Proteinstool
项目摘要
PROJECT SUMMARY/ABSTRACT
The recent wave of cryo-electron microscopy (cryo-EM) studies on amyloid fibrils has highlighted the complexity
of protein deposition amongst patients of amyloid diseases. A convincing example is found in tau, a microtubule
binding protein whose pathological aggregation causes tauopathies. Each of these tauopathies seems to be
associated with a particular structural assembly, suggesting causality. Similar to tauopathies, other amyloid
diseases manifest differential prognosis, onset, and symptomatology. This is the case of TDP-43, α-synuclein,
β-amyloid, or transthyretin (TTR), to name a few. We hypothesize that these phenotypical differences are driven
by the formation of various structural assemblies, similar to what is found in tau. As a consequence, the detection
of these disease-specific assemblies in a timely manner could ensure proper diagnosis and treatment.
We aim to map the structural spectrum of amyloid fibrils in an amyloid disease model using cryo-EM and a co-
culture system to be developed in our laboratory. Using the obtained structural information, our laboratory will
design structure-specific peptides for the detection and inhibition of amyloid fibrils in cells, mice, and patient-
derived samples. If successful, our study will serve as a launching platform for the development of personalized
structure-based diagnostics and therapeutics for amyloid diseases.
项目总结/摘要
最近一波对淀粉样纤维的冷冻电子显微镜(cryo-EM)研究突出了淀粉样纤维的复杂性,
淀粉样疾病患者的蛋白质沉积。一个令人信服的例子是在tau蛋白中发现的,
病理性聚集引起tau蛋白病的结合蛋白。每一种tau蛋白病
与一个特定的结构组合有关,表明因果关系。与tau蛋白病相似,其他淀粉样蛋白
疾病表现出不同的预后、发病和病理学。这是TDP-43,α-突触核蛋白,
β-淀粉样蛋白或甲状腺素运载蛋白(TTR),仅举几例。我们假设这些表型差异是由
通过形成各种结构组装,类似于在tau中发现的。因此,检测
这些疾病特异性组件的及时检测可以确保正确的诊断和治疗。
我们的目的是利用冷冻电镜和共聚焦显微镜,
培养系统,在我们的实验室。利用获得的结构信息,我们的实验室将
设计结构特异性肽,用于检测和抑制细胞、小鼠和患者中的淀粉样蛋白原纤维,
衍生样品。如果成功,我们的研究将作为一个启动平台,为发展个性化
淀粉样蛋白疾病的基于结构的诊断和治疗。
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)
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Lorena Saelices Gomez其他文献
Lorena Saelices Gomez的其他文献
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{{ truncateString('Lorena Saelices Gomez', 18)}}的其他基金
Closing the gap between structural biology and translational science for amyloid diseases
缩小淀粉样蛋白疾病的结构生物学和转化科学之间的差距
- 批准号:
10242433 - 财政年份:2021
- 资助金额:
$ 6.78万 - 项目类别:
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