Abramov Andrey Y, Potapova Elena V, Dremin Viktor V, Dunaev Andrey V
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Cell Physiology and Pathology Laboratory, Orel State University, Orel 302026, Russia.
Life (Basel). 2020 Jun 30;10(7):101. doi: 10.3390/life10070101.
Aggregation of the misfolded proteins β-amyloid, tau, huntingtin, and α-synuclein is one of the most important steps in the pathology underlying a wide spectrum of neurodegenerative disorders, including the two most common ones-Alzheimer's and Parkinson's disease. Activity and toxicity of these proteins depends on the stage and form of aggregates. Excessive production of free radicals, including reactive oxygen species which lead to oxidative stress, is proven to be involved in the mechanism of pathology in most of neurodegenerative disorders. Both reactive oxygen species and misfolded proteins play a physiological role in the brain, and only deregulation in redox state and aggregation of the proteins leads to pathology. Here, we review the role of misfolded proteins in the activation of ROS production from various sources in neurons and glia. We discuss if free radicals can influence structural changes of the key toxic intermediates and describe the putative mechanisms by which oxidative stress and oligomers may cause neuronal death.
错误折叠蛋白β-淀粉样蛋白、tau蛋白、亨廷顿蛋白和α-突触核蛋白的聚集是多种神经退行性疾病病理过程中最重要的步骤之一，其中包括两种最常见的疾病——阿尔茨海默病和帕金森病。这些蛋白的活性和毒性取决于聚集体的阶段和形式。事实证明，包括导致氧化应激的活性氧在内的自由基过量产生参与了大多数神经退行性疾病的病理机制。活性氧和错误折叠蛋白在大脑中均发挥生理作用，只有氧化还原状态失调和蛋白聚集才会导致病变。在此，我们综述错误折叠蛋白在神经元和神经胶质细胞中各种来源的活性氧产生激活过程中的作用。我们讨论自由基是否会影响关键毒性中间体的结构变化，并描述氧化应激和寡聚体可能导致神经元死亡的假定机制。
