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中文摘要
翻译
蛋白酶抑制作为治疗肌肉萎缩症的可能方法
英文摘要
Protease inhibition as possible therapy for muscular dystrophy The major goals of this project are to slow the loss of skeletal muscle mass and function that occurs as a consequence of the dystrophic process. Informs of muscular dystrophy in which the dystrophin and associated complex are defective (e.g. DMD, LGMD2C) or in which muscle repair is impaired (e.g. dysferlin defects), activation of muscle protein breakdown is greatly elevated. The fundamental hypothesis of this proposal is that targeted inhibition of specific proteases can reduce this elevated turnover, leading to increased muscle mass and strength. There are a number of potential targets, including intracellular proteases that are up-regulated as part of the inflammatory response, calpain and even specific arms of the ubiquitin-proteosome pathway. These pathways will be inhibited with specific drugs, alone and in combination in mouse models of muscular dystrophies. As muscular dystrophy progresses, the rate of loss of muscle accelerates as inactivity is imposed. Disuse atrophy has at its basis three major underlying causes; increased protein degradation, decreased protein synthesis and a transient component of apoptosis. These likely will greatly accelerate muscle loss on a dystrophic background. Using drugs to target specific proteases may lead to a sparing of the disuse atrophy as well as the muscle loss associated with the dystrophy itself. This will be evaluated in dystrophic mice subjected to hindlimb suspension.
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Myosin 18 and its role in skeletal muscle
  • 批准号:
    10378608
  • 项目类别:
  • 资助金额:
    $40.87万
  • 财政年份:
    2020
  • 负责人:
    H Lee Sweeney
  • 依托单位:
Myosin 18 and its role in skeletal muscle
  • 批准号:
    10599240
  • 项目类别:
  • 资助金额:
    $41.28万
  • 财政年份:
    2020
  • 负责人:
    H Lee Sweeney
  • 依托单位:
Myo10-Driven Filopodia in Skeletal Muscle
  • 批准号:
    9795646
  • 项目类别:
  • 资助金额:
    $37.6万
  • 财政年份:
    2019
  • 负责人:
    H Lee Sweeney
  • 依托单位:
Myo10-Driven Filopodia in Skeletal Muscle
  • 批准号:
    10634534
  • 项目类别:
  • 资助金额:
    $37.6万
  • 财政年份:
    2019
  • 负责人:
    H Lee Sweeney
  • 依托单位:
国内基金
海外基金
Epac1/2通过蛋白酶体调控中性粒细胞NETosis和Apoptosis在急性肺损伤中的作用研究
  • 批准号:
    LBY21H010001
  • 项目类别:
    省市级项目
  • 资助金额:
    --
  • 批准年份:
    2020
  • 负责人:
    郑绪阳
  • 依托单位:
基于Apoptosis/Ferroptosis双重激活效应的天然产物AlbiziabiosideA的抗肿瘤作用机制研究及其结构改造
  • 批准号:
    81703335
  • 项目类别:
    青年科学基金项目
  • 资助金额:
    20.0万元
  • 批准年份:
    2017
  • 负责人:
    卫高菲
  • 依托单位:
双肝移植后Apoptosis和pyroptosis在移植物萎缩差异中的作用和供受者免疫微环境变化研究
  • 批准号:
    81670594
  • 项目类别:
    面上项目
  • 资助金额:
    58.0万元
  • 批准年份:
    2016
  • 负责人:
    陈昊
  • 依托单位:
Serp-2 调控apoptosis和pyroptosis 对肝脏缺血再灌注损伤的保护作用研究
  • 批准号:
    81470791
  • 项目类别:
    面上项目
  • 资助金额:
    73.0万元
  • 批准年份:
    2014
  • 负责人:
    董家鸿
  • 依托单位: