Cork L C, Kitt C A, Struble R G, Griffin J W, Price D L
Prog Clin Biol Res. 1987;229:241-69.
Amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD) are human neurological disorders which occur in middle and late life. These three diseases share certain features: they are slowly progressive; transmitter-specific groups of neurons are selectively affected by disease processes; and affected nerve cells exhibit cytoskeletal pathology. The causes and mechanisms of cell injury are unknown, and there are no treatments which directly affect the disease process. Dysfunction and death of these specific cell groups account for different clinical syndromes. In ALS, patients become paralyzed, at-risk cholinergic motor neurons in the spinal cord develop neurofilamentous swellings of proximal axons, and distal axons atrophy. In PD, affected individuals show slowed movements, tremor, and rigidity. These clinical findings are attributed to regeneration of dopaminergic neurons of the substantia nigra, a cell group showing abnormal accumulations of neurofilament antigens in the form of Lewy bodies. In AD, patients develop dementia (a syndrome of cognitive and memory impairment), and cholinergic neurons of the basal forebrain and certain other populations of nerve cells develop abnormalities of the cytoskeleton. These include perikaryal neurofibrillary tangles and enlarged distal axons which appear as neurites in senile plaques. Certain features of ALS, PD, and AD are recapitulated in three animal models described in this review. Hereditary Canine Spinal Muscular Atrophy (HCSMA), a dominantly inherited motor neuron disease, shows many clinical and pathological features in common with ALS. Affected dogs are clinically weak, have denervation atrophy of muscles, and develop neurofilamentous swellings of proximal axons, atrophy of distal axons, and degeneration of motor neurons. These abnormalities of axonal caliber are associated with impaired transport of the neurofilament triplet proteins and a maldistribution of phosphorylated neurofilaments. Intoxication of macaques with 1-methyl-4-]henyl-1,2,3,6,tetrahydropyridine (MPTP) produces a Parkinsonian syndrome due to selective injury of dopaminergic neurons in the substantia nigra and associated denervation of the striatum. Finally, aged rhesus monkeys (older than 23 years of age) show cognitive and memory deficits and exhibit senile plaques whose neurites are derived from cholinergic and other transmitter systems. Although these macaques do not have AD, they do provide a model for examining the relationships between age-associated cognitive deficits and pathological changes occurring in certain transmitter systems of primates.(ABSTRACT TRUNCATED AT 400 WORDS)
肌萎缩侧索硬化症（ALS）、帕金森病（PD）和阿尔茨海默病（AD）是发生在中老年时期的人类神经疾病。这三种疾病有某些共同特征：它们呈缓慢进展；特定神经递质的神经元群受到疾病进程的选择性影响；受影响的神经细胞表现出细胞骨架病理变化。细胞损伤的原因和机制尚不清楚，且没有直接影响疾病进程的治疗方法。这些特定细胞群的功能障碍和死亡导致了不同的临床综合征。在ALS中，患者会瘫痪，脊髓中处于危险状态的胆碱能运动神经元近端轴突会出现神经丝肿胀，远端轴突萎缩。在PD中，患者表现出运动迟缓、震颤和僵硬。这些临床症状归因于黑质多巴胺能神经元的再生，该细胞群中出现以路易小体形式存在的神经丝抗原异常聚集。在AD中，患者会出现痴呆（一种认知和记忆障碍综合征），基底前脑的胆碱能神经元和其他某些神经细胞群会出现细胞骨架异常。这些异常包括核周神经原纤维缠结和远端轴突增粗，在老年斑中表现为神经突。本综述中描述的三种动物模型重现了ALS、PD和AD的某些特征。遗传性犬脊髓性肌萎缩症（HCSMA）是一种显性遗传的运动神经元疾病，与ALS有许多共同的临床和病理特征。患病犬在临床上表现虚弱，肌肉出现失神经萎缩，近端轴突出现神经丝肿胀，远端轴突萎缩，运动神经元退化。轴突直径的这些异常与神经丝三联体蛋白的运输受损以及磷酸化神经丝的分布不均有关。用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）使猕猴中毒会导致帕金森综合征，原因是黑质中多巴胺能神经元受到选择性损伤以及纹状体相关的去神经支配。最后，老年恒河猴（23岁以上）表现出认知和记忆缺陷，并出现神经突源自胆碱能和其他神经递质系统的老年斑。尽管这些猕猴没有患AD，但它们确实为研究与年龄相关的认知缺陷和灵长类动物某些神经递质系统中发生的病理变化之间的关系提供了一个模型。（摘要截断于400字）
