Pathogenic mechanism of sporadic amyotrophic lateral sclerosis: From a perspective of inefficient GluA2 Q/R site-RNA editing and pathological TDP-43 in motor neurons

DANG Cuijiao; JIANG Wenfei; SUN Chuanhe; LIAO Weilong; PAN Weidong

doi:10.12022/jnnr.2016-0036

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Journal of Neurology and Neurorehabilitation ›› 2016, Vol. 12 ›› Issue (2) : 94-101. DOI: 10.12022/jnnr.2016-0036

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Pathogenic mechanism of sporadic amyotrophic lateral sclerosis: From a perspective of inefficient GluA2 Q/R site-RNA editing and pathological TDP-43 in motor neurons

DANG Cuijiao, JIANG Wenfei, SUN Chuanhe, LIAO Weilong, PAN Weidong

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Abstract

Inefficient glutamate receptor A2 (GluA2) Q/R site-RNA editing and related downregulation of adenosine deaminase acting on RNA2 (ADAR2) expression as well as pathological transactivation response DNA-binding protein 43-kD (TDP-43) can simultaneously occur in the same motor neurons in patients with amyotrophic lateral sclerosis (ALS), suggesting that there may be an association among these molecular abnormalities in ALS patients. The animal experiment has found that after knock-down of ADAR2 gene, the motor neurons of the rats showed a chronic death. The abnormal mislocalization and aggregation of TDP-43 fragments induced by ADAR2 difficiency results in nerve cell toxicity, then accelerating the degeneration and death of the motor neurons. This paper summarizes the role of inefficient GluA2 Q/R site-RNA editing and TDP-43 pathology in sporadic ALS, and discusses the possible influencing factors associated with inefficient RNA editing mediated by ADAR2, hoping to provide useful information to develop a novel therapeutic strategy for ALS.

Key words

Amyotrophic lateral sclerosis / Glutamate receptor / TDP-43 / Calpain / Pathogenic mechanism

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DANG Cuijiao, JIANG Wenfei, SUN Chuanhe, LIAO Weilong, PAN Weidong. Pathogenic mechanism of sporadic amyotrophic lateral sclerosis: From a perspective of inefficient GluA2 Q/R site-RNA editing and pathological TDP-43 in motor neurons[J]. Journal of Neurology and Neurorehabilitation. 2016, 12(2): 94-101 https://doi.org/10.12022/jnnr.2016-0036

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