Alpha-synuclein and beta-amyloid different targets, same players: calcium, free radicals and mitochondria in the mechanism of neurodegeneration
Alpha-synuclein and beta-amyloid different targets, same players: calcium, free radicals and mitochondria in the mechanism of neurodegeneration
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DOI：
10.1016/j.bbrc.2016.07.103
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发表时间：
2017-02-19
影响因子：
3.1
通讯作者：
Abramov, Andrey Y.
中科院分区：
文献类型：
--
作者：
Angelova, Plamena R.;Abramov, Andrey Y.
两种最具破坏性的神经退行性疾病是关键蛋白质-α突触核蛋白和β淀粉样蛋白的错误折叠和聚集的结果。虽然这两种蛋白质的主要靶点不同，但它们都有一个共同的机制，即在质膜上形成孔样结构，随后钙稳态失调，线粒体功能障碍和氧化损伤。所有这些因素的综合作用最终导致神经元细胞死亡。β淀粉样蛋白作用于星形胶质细胞质膜，表现出对膜胆固醇含量的紧密依赖性，而α突触核蛋白不能区分膜或细胞的类型。此外，两种蛋白质的寡聚体形式通过不同的机制产生活性氧：β-淀粉样蛋白通过NADPH氧化酶的激活和α-突触核蛋白通过非酶促方式。最后，两种寡聚体形式的肽通过钙超载和自由基产生诱导线粒体去极化，最终导致线粒体渗透性转换孔的打开并触发细胞死亡。(C)2016 Elsevier Inc. All rights reserved.
Two of the most devastating neurodegenerative diseases are consequences out of misfolding and aggregation of key proteins-alpha synuclein and beta-amyloid. Although the primary targets for the two proteins are different, they both share a common mechanism that involves formation of pore-like structure on the plasma membrane, consequent dysregulation of calcium homeostasis, mitochondrial dysfunction and oxidative damage. The combined effect of all this factors ultimately leads to neuronal cell death. Whereas beta amyloid acts on the astrocytic plasma membrane, exhibiting a tight dependence to the membrane cholesterol content, alpha synuclein does not distinguish between type of membrane or cell. Additionally, oligomeric forms of both proteins produce reactive oxygen species through different" mechanisms: beta-amyloid through activation of the NADPH oxidase and alpha-synuclein through non enzymatic way. Finally, both peptides in oligomeric form induce mitochondrial depolarisation through calcium overload and free radical production that ultimately lead to opening of the mitochondrial permeability transition pore and trigger cell death. (C) 2016 Elsevier Inc. All rights reserved.