Morrison B M, Hof P R, Morrison J H
Neurobiology of Aging Laboratories and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Ann Neurol. 1998 Sep;44(3 Suppl 1):S32-44. doi: 10.1002/ana.410440706.
Selective neuronal vulnerability can be defined anatomically by the differential vulnerability of circuits and neurochemically by the vulnerability of neurons that differentially express particular proteins. The anatomic perspective is exemplified by the vulnerability of the nigrostriatal projection in Parkinson's disease (PD), the degeneration of upper and lower motor neurons in amyotrophic lateral sclerosis (ALS), and the preferential loss of long corticocortical projections in Alzheimer's disease (AD). The neurochemical perspective is reflected in the heightened vulnerability of neurons that normally express high somatodendritic levels of neurofilament (eg, entorhinal and association cortices in AD, the spinal cord in a mouse model of ALS, and the retina in a primate model of glaucoma), as well as the reduced vulnerability of neurons that express calcium-binding proteins (eg, neocortex of AD patients, the spinal cord and brainstem of ALS patients, and the spinal cord of a mouse model of ALS). By combining neurochemical and anatomic correlates of vulnerability, an integrated view of vulnerable neurons is emerging in which characteristics of vulnerable neurons appear to transcend both brain region and disease state, suggesting that neurodegenerative disorders share common mechanisms of degeneration.
选择性神经元易损性在解剖学上可通过不同回路的易损性来定义，在神经化学上可通过差异表达特定蛋白质的神经元的易损性来定义。解剖学观点的例证包括帕金森病（PD）中黑质纹状体投射的易损性、肌萎缩侧索硬化症（ALS）中上下运动神经元的退化以及阿尔茨海默病（AD）中长距离皮质-皮质投射的优先丧失。神经化学观点体现在通常在胞体树突表达高水平神经丝的神经元的更高易损性（例如，AD中的内嗅皮质和联合皮质、ALS小鼠模型中的脊髓以及青光眼灵长类动物模型中的视网膜），以及表达钙结合蛋白的神经元的较低易损性（例如，AD患者的新皮质、ALS患者的脊髓和脑干以及ALS小鼠模型的脊髓）。通过结合易损性的神经化学和解剖学相关性，一种关于易损神经元的综合观点正在形成，其中易损神经元的特征似乎超越了脑区和疾病状态，这表明神经退行性疾病具有共同的退化机制。
