Dugger Brittany N, Dickson Dennis W
Institute for Neurodegenerative Diseases, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94143.
Mayo Clinic, Jacksonville, Florida 32224.
Cold Spring Harb Perspect Biol. 2017 Jul 5;9(7):a028035. doi: 10.1101/cshperspect.a028035.
Neurodegenerative disorders are characterized by progressive loss of selectively vulnerable populations of neurons, which contrasts with select static neuronal loss because of metabolic or toxic disorders. Neurodegenerative diseases can be classified according to primary clinical features (e.g., dementia, parkinsonism, or motor neuron disease), anatomic distribution of neurodegeneration (e.g., frontotemporal degenerations, extrapyramidal disorders, or spinocerebellar degenerations), or principal molecular abnormality. The most common neurodegenerative disorders are amyloidoses, tauopathies, α-synucleinopathies, and TDP-43 proteinopathies. The protein abnormalities in these disorders have abnormal conformational properties. Growing experimental evidence suggests that abnormal protein conformers may spread from cell to cell along anatomically connected pathways, which may in part explain the specific anatomical patterns observed at autopsy. In this review, we detail the human pathology of select neurodegenerative disorders, focusing on their main protein aggregates.
神经退行性疾病的特征是选择性易损神经元群体的渐进性丧失，这与因代谢或毒性疾病导致的选择性静态神经元丧失形成对比。神经退行性疾病可根据主要临床特征（如痴呆、帕金森综合征或运动神经元病）、神经退行性变的解剖分布（如额颞叶变性、锥体外系疾病或脊髓小脑变性）或主要分子异常进行分类。最常见的神经退行性疾病是淀粉样变性、tau蛋白病、α-突触核蛋白病和TDP-43蛋白病。这些疾病中的蛋白质异常具有异常的构象特性。越来越多的实验证据表明，异常蛋白质构象异构体可能沿着解剖学上相连的途径在细胞间传播，这可能部分解释了尸检时观察到的特定解剖模式。在这篇综述中，我们详细阐述了某些神经退行性疾病的人体病理学，重点关注其主要蛋白质聚集体。
