肌萎缩性侧索硬化症(ALS)是成人最常见的神经退行性疾病之一,其特征是大脑皮层运动神经元的进行性死亡,脑干和脊髓.运动神经元的功能障碍和死亡导致进行性肌肉无力,萎缩,束感,痉挛,最终导致整个身体瘫痪。尽管已经发现了几种与ALS发病机制相关的基因突变,包括9号染色体开放阅读框72中导致GGGGCC重复序列异常扩增的突变,TARDNA结合蛋白43,在肉瘤中融合/在脂肪肉瘤中易位,铜/锌超氧化物歧化酶1(SOD1)和TANK结合激酶1,导致ALS的运动神经元特定变性的确切机制仍未完全了解。目前,由于建立了表达SOD1突变体的转基因模型,已经开发了多个ALS的体外模型来研究病理学,ALS的病理生理学和发病机制以及寻找有效的神经治疗方法。本文综述了目前建立的用于病理学研究的体外模型的细节,ALS的病理生理学和发病机制。同时,我们还讨论了优势,缺点,每个模型的成本和可用性。
Amyotrophic Lateral Sclerosis (ALS) is one of the commonest neurodegenerative diseases of adult-onset, which is characterized by the progressive death of motor neurons in the cerebral cortex, brain stem and spinal cord. The dysfunction and death of motor neurons lead to the progressive muscle weakness, atrophy, fasciculations, spasticity and ultimately the whole paralysis of body. Despite the identification of several genetic mutations associated with the pathogenesis of ALS, including mutations in chromosome 9 open reading frame 72 leading to the abnormal expansion of GGGGCC repeat sequence, TAR DNA-binding protein 43, fused in sarcoma/translocated in liposarcoma, copper/zinc superoxide dismutase 1 (SOD1) and TANK-binding kinase 1, the exact mechanisms underlying the specific degeneration of motor neurons that causes ALS remain incompletely understood. At present, since the transgenic model expressed SOD1 mutants was established, multiple in vitro models of ALS have been developed for studying the pathology, pathophysiology and pathogenesis of ALS as well as searching the effective neurotherapeutics. This review reviewed the details of present established in vitro models used in studying the pathology, pathophysiology and pathogenesis of ALS. Meanwhile, we also discussed the advantages, disadvantages, cost and availability of each models.