Role of mitochondrial-mediated signaling pathways in Alzheimer disease and hypoxia.

Role of mitochondrial-mediated signaling pathways in Alzheimer disease and hypoxia.
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DOI:
10.1007/s10863-009-9247-1
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发表时间:
2009-10
影响因子:
3
通讯作者:
Perry, George
Perry, George
中科院分区:
生物学4区
文献类型:
--
作者:
Carvalho, Cristina;Correia, Sonia C.;Santos, Renato X.;Cardoso, Susana;Moreira, Paula I.;Clark, Timothy A.;Zhu, Xiongwei;Smith, Mark A.;Perry, George
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阿尔茨海默病的有效治疗方法的发展由于对其病理生理学的缺乏了解而变得复杂。最近的研究表明,由于线粒体周转的改变,线粒体可能在神经退化中发挥主要作用,而且由于高能量需求,大脑特别容易受到影响。线粒体通过氧化磷酸化是细胞能量的主要来源,并调节细胞内钙水平和生存途径。缺氧与包括阿尔茨海默病在内的几种神经退行性疾病有关。在低氧事件中,线粒体复合体III产生高水平的活性氧物种(ROS)。这些ROS似乎在转录因子低氧诱导因子1α的调节中起主要作用,该转录因子可触发死亡效应。在这里,我们讨论线粒体在AD中的作用,重点放在低氧介导的线粒体通路的激活,最终可能导致细胞退化和死亡。
Development of effective treatments for Alz-heimer’s disease is complicated by the poor understanding of its pathophysiology. Recent work suggests mitochondria may play a primary role in neurodegeneration, due to alterations in mitochondria turnover and that the brain is specifically susceptible, due to high energy demand. Mitochondria are the major source of cellular energy through oxidative phosphorylation and regulate intracellular calcium levels and survival pathways. Hypoxia has been implicated in several neurodegenerative diseases including Alzheimer’s disease. During hypoxic events, mitochondrial complex III produces high levels of reactive oxygen species (ROS). These ROS seem to have a primary role in the regulation of the transcription factor hypoxia inducible factor 1α that triggers death effectors. Here we discuss the role of mitochondria in AD putting focus on the activation of hypoxia-mediated mitochondrial pathways, which could eventually lead to cell degeneration and death.
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