Structure and Genesis of tau Aggregates

tau 聚集体的结构和成因

基本信息

  • 批准号:
    10522274
  • 负责人:
  • 金额:
    $ 182.17万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-06-01 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Tau aggregation is a shared pathology of Alzheimer's disease and related dementias known as tauopathies. Despite commonalities in aggregation mechanism, each disorder develops unique filamentous morphologies that reflect differential vulnerability of their constituent cell populations. In addition to providing clues about the cellular conditions associated with tauopathic neurodegeneration, the appearance of unique polymorphs in each tauopathy implicates prion-like mechanisms of templating and spread that may influence the course and severity of disease. As a result, aggregate polymorphism is a potential target for therapeutic intervention as well as for differential diagnosis of tauopathies through development of whole-brain imaging methods. This proposal seeks to advance these goals by clarifying mechanisms underlying aggregate nucleation, propagation and interaction with small-molecule probes using biochemical and structural biological approaches. Specifically it aims to (1) determine the effects of aggregation inducers including tau phosphorylation on polymorph formation, (2) clarify mechanisms through which nucleation sequence motifs common to all tau isoforms trigger aggregation, (3) rigorously test whether tau polymorphism can propagate through prion-like seeding mechanisms, and (4) identify molecular interactions that mediate the binding affinity and selectivity of tau-aggregate directed ligands. Accomplishing these goals will clarify the molecular basis of tauopathy pathogenesis and catalyze efforts toward creating novel diagnostic strategies tailored toward individual tau aggregate polymorphs.
项目总结

项目成果

期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Identification of gene networks mediating regional resistance to tauopathy in late-onset Alzheimer's disease.
鉴定基因网络,介导了晚期阿尔茨海默氏病中对tauopathy的区域抗性。
  • DOI:
    10.1371/journal.pgen.1010681
  • 发表时间:
    2023-03
  • 期刊:
  • 影响因子:
    4.5
  • 作者:
  • 通讯作者:
Computational integration of nanoscale physical biomarkers and cognitive assessments for Alzheimer's disease diagnosis and prognosis.
  • DOI:
    10.1126/sciadv.1700669
  • 发表时间:
    2017-07
  • 期刊:
  • 影响因子:
    13.6
  • 作者:
    Yue T;Jia X;Petrosino J;Sun L;Fan Z;Fine J;Davis R;Galster S;Kuret J;Scharre DW;Zhang M
  • 通讯作者:
    Zhang M
A New Approach for Estimating the Free Energy Differences among Multiple Thermodynamic States in Statistical Simulations.
估计统计模拟中多个热力学状态之间的自由能差异的新方法。
A liquid chromatography tandem mass spectroscopy approach for quantification of protein methylation stoichiometry.
用于定量蛋白质甲基化化学计量的液相色谱串联质谱方法。
  • DOI:
    10.1016/j.ab.2018.01.018
  • 发表时间:
    2018
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Cooper,GraceL;Huseby,CarolJ;Chandler,ClaireN;Cocuron,Jean-Christophe;Alonso,AnaP;Kuret,Jeff
  • 通讯作者:
    Kuret,Jeff
A theoretical study of polymorphism in VQIVYK fibrils.
VQIVYK原纤维多态性的理论研究。
  • DOI:
    10.1016/j.bpj.2021.01.032
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Yang,Jaehoon;Agnihotri,MithilaV;Huseby,CarolJ;Kuret,Jeff;Singer,SherwinJ
  • 通讯作者:
    Singer,SherwinJ
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Jeff Kuret其他文献

Jeff Kuret的其他文献

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{{ truncateString('Jeff Kuret', 18)}}的其他基金

Structure and Genesis of tau Aggregates
tau 聚集体的结构和成因
  • 批准号:
    9311789
  • 财政年份:
    2017
  • 资助金额:
    $ 182.17万
  • 项目类别:
Structure and Genesis of tau Aggregates
tau 聚集体的结构和成因
  • 批准号:
    10158623
  • 财政年份:
    2017
  • 资助金额:
    $ 182.17万
  • 项目类别:
Imaging agents for synucleinopathy drug discovery
用于突触核蛋白病药物发现的显像剂
  • 批准号:
    9182629
  • 财政年份:
    2016
  • 资助金额:
    $ 182.17万
  • 项目类别:
Imaging agents for synucleinopathy drug discovery
用于突触核蛋白病药物发现的显像剂
  • 批准号:
    9318582
  • 财政年份:
    2016
  • 资助金额:
    $ 182.17万
  • 项目类别:
The tau code of Alzheimer's disease
阿尔茨海默病的 tau 密码
  • 批准号:
    8484896
  • 财政年份:
    2012
  • 资助金额:
    $ 182.17万
  • 项目类别:
The tau code of Alzheimer's disease
阿尔茨海默病的 tau 密码
  • 批准号:
    8399904
  • 财政年份:
    2012
  • 资助金额:
    $ 182.17万
  • 项目类别:
STRUCTURE, FUNCTION, AND REGULATION OF CASEIN KINASE-1
酪蛋白激酶-1 的结构、功能和调控
  • 批准号:
    6386731
  • 财政年份:
    1997
  • 资助金额:
    $ 182.17万
  • 项目类别:
STRUCTURE, FUNCTION, AND REGULATION OF CASEIN KINASE-1
酪蛋白激酶-1 的结构、功能和调控
  • 批准号:
    6031731
  • 财政年份:
    1997
  • 资助金额:
    $ 182.17万
  • 项目类别:
STRUCTURE AND GENESIS OF TAU FILAMENTS
TAU 丝的结构和起源
  • 批准号:
    2683182
  • 财政年份:
    1997
  • 资助金额:
    $ 182.17万
  • 项目类别:
STRUCTURE AND GENESIS OF TAU FILAMENTS
TAU 丝的结构和起源
  • 批准号:
    2002359
  • 财政年份:
    1997
  • 资助金额:
    $ 182.17万
  • 项目类别:

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