Mitochondrial dysfunction and cellular metabolic deficiency in Alzheimer’s disease
Mitochondrial dysfunction and cellular metabolic deficiency in Alzheimer’s disease
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DOI：
10.1007/s12264-012-1270-2
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发表时间：
2012-09
影响因子：
5.6
通讯作者：
Xue-mei Gu;Han-Chang Huang;Zhao-feng Jiang
中科院分区：
文献类型：
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作者：
Xue-mei Gu;Han-Chang Huang;Zhao-feng Jiang
阿尔茨海默病（AD）是一种与年龄相关的神经退行性疾病。 AD 的病理包括神经炎斑块中的淀粉样蛋白-β (Aβ) 沉积和由过度磷酸化的 tau 蛋白组成的神经原纤维缠结，以及特定大脑区域的神经元损失。越来越多的流行病学和功能性神经影像学证据表明，大脑代谢的整体和区域破坏与这种疾病的发病机制有关。 Aβ 前体蛋白被裂解产生细胞外和细胞内 Aβ，其积累可能会干扰细胞代谢的稳态。线粒体是高度动态的细胞器，不仅为细胞提供主要能量，还调节细胞凋亡。线粒体功能障碍可能导致 Aβ 神经毒性。在这篇综述中，我们总结了 Aβ 生成的途径及其对细胞代谢和线粒体功能障碍的潜在神经毒性作用。
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder. The pathology of AD includes amyloid-β (Aβ) deposits in neuritic plaques and neurofibrillary tangles composed of hyperphosphorylated tau, as well as neuronal loss in specific brain regions. Increasing epidemiological and functional neuroimaging evidence indicates that global and regional disruptions in brain metabolism are involved in the pathogenesis of this disease. Aβ precursor protein is cleaved to produce both extracellular and intracellular Aβ, accumulation of which might interfere with the homeostasis of cellular metabolism. Mitochondria are highly dynamic organelles that not only supply the main energy to the cell but also regulate apoptosis. Mitochondrial dysfunction might contribute to Aβ neurotoxicity. In this review, we summarize the pathways of Aβ generation and its potential neurotoxic effects on cellular metabolism and mitochondrial dysfunction.