Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
J Cell Biol. 2009 Dec 14;187(6):761-72. doi: 10.1083/jcb.200908164.
Selective degeneration and death of one or more classes of neurons is the defining feature of human neurodegenerative disease. Although traditionally viewed as diseases mainly affecting the most vulnerable neurons, in most instances of inherited disease the causative genes are widely-usually ubiquitously-expressed. Focusing on amyotrophic lateral sclerosis (ALS), especially disease caused by dominant mutations in Cu/Zn superoxide dismutase (SOD1), we review here the evidence that it is the convergence of damage developed within multiple cell types, including within neighboring nonneuronal supporting cells, which is crucial to neuronal dysfunction. Damage to a specific set of key partner cells as well as to vulnerable neurons may account for the selective susceptibility of neuronal subtypes in many human neurodegenerative diseases, including Huntington's disease (HD), Parkinson's disease (PD), prion disease, the spinal cerebellar ataxias (SCAs), and Alzheimer's disease (AD).
选择性的一个或多个神经元群体的退化和死亡是人类神经退行性疾病的特征。虽然传统上认为这些疾病主要影响最脆弱的神经元，但在大多数遗传性疾病的情况下，致病基因是广泛表达的，通常是普遍表达的。以肌萎缩性侧索硬化症（ALS），特别是由铜/锌超氧化物歧化酶（SOD1）的显性突变引起的疾病为例，我们在这里回顾了这样一个证据，即多种细胞类型（包括邻近的非神经元支持细胞）内的损伤的汇聚对于神经元功能障碍至关重要。特定一组关键的伴侣细胞以及脆弱神经元的损伤可能解释了许多人类神经退行性疾病中神经元亚型的选择性易感性，包括亨廷顿病（HD）、帕金森病（PD）、朊病毒病、脊髓小脑共济失调（SCAs）和阿尔茨海默病（AD）。
