Nutrient excess and altered mitochondrial proteome and function contribute to neurodegeneration in diabetes.

Nutrient excess and altered mitochondrial proteome and function contribute to neurodegeneration in diabetes.
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DOI:
10.1016/j.mito.2011.06.007
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发表时间:
2011-11
期刊:
影响因子:
4.4
通讯作者:
Femyhough, Paul
Femyhough, Paul
中科院分区:
生物学3区
文献类型:
--
作者:
Chowdhury, Subir K. Roy;Dobrowsky, Rick T.;Femyhough, Paul

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糖尿病神经病变是糖尿病的主要并发症,会导致感觉神经系统的进行性恶化。线粒体功能障碍被认为在糖尿病神经病变的神经退行性变的发病机制中起重要作用。我们最近的工作表明,在链脲佐菌素(STZ)诱导的糖尿病啮齿动物中,背根神经节(DRG)感觉神经元存在线粒体功能障碍。在神经元中,与长期糖尿病相关的营养过剩可能触发AMPK和/或沉默的信息调节因子T1(SIRT1)信号的关闭,导致过氧化体增殖物激活受体γ辅活化子-1α(PGC-1α)表达/活性受损,线粒体活性降低。本文简要综述了STZ糖尿病啮齿动物感觉神经元线粒体功能和蛋白质组的变化。我们还讨论了AMPK/SIRT/PGC-1α通路在其他糖尿病模型和糖尿病影响的不同组织中的可能参与。
Diabetic neuropathy is a major complication of diabetes that results in the progressive deterioration of the sensory nervous system. Mitochondrial dysfunction has been proposed to play an important role in the pathogenesis of the neurodegeneration observed in diabetic neuropathy. Our recent work has shown that mitochondrial dysfunction occurs in dorsal root ganglia (DRG) sensory neurons in streptozotocin (STZ) induced diabetic rodents. In neurons, the nutrient excess associated with prolonged diabetes may trigger a switching off of AMP kinase (AMPK) and/or silent information regulator T1 (SIRT1) signaling leading to impaired peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α expression/activity and diminished mitochondrial activity. This review briefly summarizes the alterations of mitochondrial function and proteome in sensory neurons of STZ-diabetic rodents. We also discuss the possible involvement of AMPK/SIRT/PGC-1α pathway in other diabetic models and different tissues affected by diabetes.
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