Neurotoxicity Research

, Volume 34, Issue 1, pp 109–120 | Cite as

Autophagic Modulation by Trehalose Reduces Accumulation of TDP-43 in a Cell Model of Amyotrophic Lateral Sclerosis via TFEB Activation

  • Ying Wang
  • Feng-Tao Liu
  • Yi-Xuan Wang
  • Rong-Yuan Guan
  • Chen Chen
  • Da-Ke Li
  • Lu-Lu Bu
  • Jie Song
  • Yu-Jie Yang
  • Yi Dong
  • Yan Chen
  • Jian Wang


Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease characterized by the formation of protein inclusion and progressive loss of motor neurons, finally leading to muscle weakness and respiratory failure. So far, the effective drugs for ALS are yet to be developed. Impairment of transcriptional activator transcription factor EB (TFEB) has been demonstrated as a key element in the pathogenesis of ALS. Trehalose is an mechanistic target of rapamycin-independent inducer for autophagy, which showed autophagic activation and neuroprotective effect in a variety of neurodegenerative diseases. The mechanism for trehalose-induced autophagy enhancement is not clear, and its therapeutic effect on TAR DNA-binding protein-43 (TDP-43) proteinopathies has been poorly investigated. Here we examined the effect of trehalose on TDP-43 clearance in a cell culture model and identified that trehalose treatment significantly reduced TDP-43 accumulation in vitro through modulation of the autophagic degradation pathway. Further studies revealed that activation of TFEB induced by trehalose was responsible for the enhancement of autophagy and clearance of TDP-43 level. These results gave us the notion that TFEB is a central regular in trehalose-mediated autophagic clearance of TDP-43 aggregates, representing an important step forward in the treatment of TDP-43 related ALS diseases.


Amyotrophic lateral sclerosis Autophagy TDP-43 TFEB Trehalose 



This work was supported by grants to Jian Wang from the National Natural Science Foundation of China (81571232 and 81371413) and project (2016YFC1306500) from the Ministry of Science and Technology of China, and grants to Feng-Tao Liu from Scientific Research Project (2016QD01) from Huashan Hospital affiliated to Fudan University. The authors wish to express their gratitude to Professor Jin Xu and his laboratory members for their guidance and technical assistance.

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflicts of interest.


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Authors and Affiliations

  1. 1.Department of Neurology & National Clinical Research Center for Aging and Medicine, Huashan HospitalFudan UniversityShanghaiChina
  2. 2.Department of Neurology, Shanghai East HospitalTongji University School of MedicineShanghaiChina

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