1Advanced Institute of Translational Medicine, Tongji University, Shanghai 200092, China
2East Hospital, Tongji University School of Medicine, Shanghai 200120, China
3Tianjin Hospital, Tianjin Academy of Integrative Medicine, Tianjin 300211, China
*These authors contributed equally to this work.
Corresponding authors: Jun Xu and Hongwen Zhu. E-mail: xunymc2000@yahoo.com; hongwen_zhu@hotmail.com

Abstract 

Autophagy is the main catabolic pathway in cells for the degradation of impaired proteins and organelles. Accumulating evidence supports the hypothesis that dysfunction of autophagy, leading to an imbalance of proteostasis and the accumulation of toxic proteins in neurons, is a central player in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). The clinical pathology of ALS is complex and many genes associated with autophagy and RNA processing are mutated in patients with the familial form. But a causal relationship between autophagic dysfunction and ALS has not been fully established. More importantly, studies on the pathological mechanism of ALS are mainly based on animal models that may not precisely recapitulate the disease itself in human beings. The development of human iPSC techniques allows us to address these issues directly in human cell models that may profoundly infl uence drug discovery for ALS.

Keywords

motor neuron disease; iPSC; autophagy; amyotrophic lateral sclerosis; spinal muscular atrophy

[SpringerLink]