Amyloid toxicity in Alzheimer's disease
Amyloid toxicity in Alzheimer's disease
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DOI：
10.1515/revneuro-2017-0063
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发表时间：
2018-08-01
影响因子：
4.1
通讯作者：
Kasselman, Lora J.
中科院分区：
文献类型：
--
作者：
Reiss, Allison B.;Arain, Hirra A.;Kasselman, Lora J.
阿尔茨海默病（AD）病理学的主要特征是由聚集的淀粉样蛋白-β（A β）肽组成的斑块。虽然这些斑块可能具有有害的性质，但有许多证据表明可溶性寡聚体A β是主要的有害形式。β寡聚体可以在细胞外和细胞内产生。β对神经元的毒性有很多种。它可以导致孔隙形成，导致离子泄漏，破坏细胞钙平衡和膜电位损失。它可以促进细胞凋亡，导致突触丢失，破坏细胞骨架。目前AD的治疗是有限的和姑息性的。许多研究和努力致力于减少A β的产生，作为减缓或预防AD发展的方法。β形成是由人淀粉样前体蛋白（APP）的淀粉样裂解引起的。通过减少APP或抑制将前体蛋白转化为淀粉样蛋白的酶，重新配置这一过程以不利于淀粉样蛋白的产生是可能的。
A major feature of Alzheimer's disease (AD) pathology is the plaque composed of aggregated amyloid-beta (A beta) peptide. Although these plaques may have harmful properties, there is much evidence to implicate soluble oligomeric A beta as the primary noxious form. A beta oligomers can be generated both extracellularly and intracellularly. A beta is toxic to neurons in a myriad of ways. It can cause pore formation resulting in the leakage of ions, disruption of cellular calcium balance, and loss of membrane potential. It can promote apoptosis, cause synaptic loss, and disrupt the cytoskeleton. Current treatments for AD are limited and palliative. Much research and effort is being devoted to reducing A beta production as an approach to slowing or preventing the development of AD. A beta formation results from the amyloidogenic cleavage of human amyloid precursor protein (APP). Reconfiguring this process to disfavor amyloid generation might be possible through the reduction of APP or inhibition of enzymes that convert the precursor protein to amyloid.