Institute of Clinical Neurobiology, Kenyongasse, Vienna, Austria.
J Cell Mol Med. 2010 Mar;14(3):457-87. doi: 10.1111/j.1582-4934.2010.01010.x. Epub 2010 Jan 11.
Neurodegenerative diseases are characterized by progressive dysfunction of specific populations of neurons, determining clinical presentation. Neuronal loss is associated with extra and intracellular accumulation of misfolded proteins, the hallmarks of many neurodegenerative proteinopathies. Major basic processes include abnormal protein dynamics due to deficiency of the ubiquitin-proteosome-autophagy system, oxidative stress and free radical formation, mitochondrial dysfunction, impaired bioenergetics, dysfunction of neurotrophins, 'neuroinflammatory' processes and (secondary) disruptions of neuronal Golgi apparatus and axonal transport. These interrelated mechanisms lead to programmed cell death is a long run over many years. Neurodegenerative disorders are classified according to known genetic mechanisms or to major components of protein deposits, but recent studies showed both overlap and intraindividual diversities between different phenotypes. Synergistic mechanisms between pathological proteins suggest common pathogenic mechanisms. Animal models and other studies have provided insight into the basic neurodegeneration and cell death programs, offering new ways for future prevention/treatment strategies.
神经退行性疾病的特征是特定神经元群体的进行性功能障碍，决定了临床表现。神经元丧失与错误折叠蛋白质的细胞内外积累有关，这是许多神经退行性蛋白病的标志。主要的基本过程包括由于泛素蛋白酶体自噬系统缺乏、氧化应激和自由基形成、线粒体功能障碍、生物能障碍、神经营养因子功能障碍、“神经炎症”过程以及（继发性）神经元高尔基体和轴突运输中断引起的异常蛋白质动力学。这些相互关联的机制导致程序性细胞死亡是一个长期的过程，跨越许多年。神经退行性疾病根据已知的遗传机制或主要的蛋白质沉积成分进行分类，但最近的研究表明，不同表型之间存在重叠和个体内多样性。病理蛋白之间的协同机制提示存在共同的致病机制。动物模型和其他研究为基础的神经退行性变和细胞死亡程序提供了深入的了解，为未来的预防/治疗策略提供了新的途径。
