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Dong et al. Neuroimmunol Neuroinflammation 2018;5:5 Neuroimmunology and
DOI: 10.20517/2347-8659.2017.47 Neuroinflammation

Review Open Access

The role of ubiquitinated TDP-43 in amyotrophic
lateral sclerosis

Yi Dong, Yan Chen

Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Correspondence to: Dr. Yan Chen, Department of Neurology, Huashan Hospital, Fudan University, No. 12 Middle Wulumuqi Road,
Jinan District, Shanghai 200040, China. E-mail: chhyann@163.com
How to cite this article: Dong Y, Chen Y. The role of ubiquitinated TDP-43 in amyotrophic lateral sclerosis. Neuroimmunol
Neuroinflammation 2018;5:5. http://dx.doi.org/10.20517/2347-8659.2017.47
Received: 3 Sep 2017 Frist Decision: 19 Jan 2018 Revised: 30 Jan 2018 Accepted: 31 Jan 2018 Published: 26 Feb 2018

Science Editor: Athanassios P. Kyritsis Copy Editor: Jun-Yao Li Production Editor: Huan-Liang Wu

Abstract
Deposition of intracellular ubiquitin inclusion in motor neurons is one of the leading pathogenic mechanisms of
amyotrophic lateral sclerosis (ALS). The transactive response DNA binding protein-43 (TDP-43) is the main component
of intracellular ubiquitin inclusion bodies in pathological deposits. TDP-43 is mainly distributed in the nucleus of
neurons, and participates in nuclear RNA transcription, alternative splicing and mRNA stability regulation. The tardbp,
as a coding gene, provides instructions for making TDP-43. After post-translational modification, the pathological
TDP-43 induces pathological deposition in cells and is associated with neurodegenerative diseases, which is similar to
tau in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease. The pathogenic tardbp mutation can affect the
localization of reverse transcription in the cell. This review summarizes the mechanisms underlying the pathogenesis of
ALS by ubiquitination of TDP-43 protein.

Keywords: TDP-43 protein, ubiquitination, tardbp, amyotrophic lateral sclerosis

INTRODUCTION
Amyotrophic lateral sclerosis (ALS) is a disease of progressive degeneration of motor neurons with an
insidious onset. It is fatal due to progressive weaking of respiratory muscles. Lack of effective treatment
has frustrated the medical community, and the underlying mechanism of ALS remains undetermined.
[1]
Following the discovery of superoxidase dismutase 1 (SOD1) mutation in familial ALS , TAR DNA-
[2]
binding protein 43 (tdp43/tardbp) inclusions have been found in ALS to be related to familial ALS (fALS).
Moreover, TDP-43 protein, as an intracellular ubiquitin inclusion, has also been identified in sporadic ALS
[3,4]
patients . The understanding of the pathogenic mechanism of ALS has been gradually changed by the
© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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