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多发性硬化症和阿尔茨海默病之间共有的神经退行性变机制。

Mechanisms of neurodegeneration shared between multiple sclerosis and Alzheimer's disease.

机构信息

Center for Brain Research, Medical University of Vienna, Wien, Austria.

出版信息

J Neural Transm (Vienna). 2011 May;118(5):747-52. doi: 10.1007/s00702-011-0607-8. Epub 2011 Mar 5.

Abstract

Multiple sclerosis and Alzheimer's disease are fundamentally different diseases. However, recent data suggest that certain mechanisms of neurodegeneration may be shared between the two diseases. Inflammation drives the disease in multiple sclerosis. It is also present in Alzheimer's disease lesions, where it may have dual functions in amyloid clearance as well as in the propagation of neurodegeneration. In both diseases, degeneration of neurons, axons, and synapses occur on the background of profound mitochondrial injury. Reactive oxygen and nitric oxide intermediates are major candidates for the induction of mitochondrial injury. Radicals are produced through the induction of the respiratory burst in activated microglia, which are present in the lesions of both diseases. In addition, liberation of toxic iron from intracellular stores may augment radical formation. Finally reactive oxygen species are also produced in the course of mitochondrial injury itself. Anti-oxidant and mitochondria protective therapeutic strategies may be beneficial both in multiple sclerosis and Alzheimer's disease in particular in early stages of the disease.

摘要

多发性硬化症和阿尔茨海默病是两种完全不同的疾病。然而,最近的数据表明,两种疾病之间可能存在某些神经退行性变的共同机制。炎症驱动多发性硬化症的发病。它也存在于阿尔茨海默病病变中,在那里它可能在清除淀粉样蛋白以及神经退行性变的传播中具有双重功能。在这两种疾病中,神经元、轴突和突触的退化都发生在深刻的线粒体损伤的背景下。活性氧和一氧化氮中间体是诱导线粒体损伤的主要候选物。自由基是通过激活的小胶质细胞呼吸爆发诱导产生的,而小胶质细胞存在于这两种疾病的病变中。此外,细胞内储存的有毒铁的释放也可能增加自由基的形成。最后,活性氧也在线粒体损伤本身的过程中产生。抗氧化和线粒体保护治疗策略在多发性硬化症和阿尔茨海默病中可能都是有益的,特别是在疾病的早期阶段。

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