In Vitro Models of Amyotrophic Lateral Sclerosis

Abstract

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.

Keywords: Amyotrophic lateral sclerosis; In vitro model; Induced pluripotent stem cells; NCS-34; Neural precursor cells; Xenopus oocyte.

Fig. 1

Categories of in vitro models of ALS. The in vitro models of ALS can be divided into two main categories. The cellular models include the primary cultures of neurons and glia, as well as established cell lines derived from the patients or the animal models of ALS. The in vitro systems models include the co-cultures of motor neurons and glia, organoids derived from human iPSCs, and microfluidic devices that mimic the flow of cerebrospinal fluid. These models are used to study the pathological mechanism of ALS, meanwhile, to test the efficacy of potential therapies. iPSCs induced pluripotent stem cells, NPCs neural precursor cells, ALS amyotrophic lateral sclerosis

Fig. 2

The most common in vitro models of ALS. iPSCs induced pluripotent stem cells, NPCs neural precursor cells, Nsc-34 neuroblastoma-spinal cord-34, ALS amyotrophic lateral sclerosis

Fig. 3

The pros and cons of the most common in vitro models of ALS