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Aberrant activation of AMP-activated protein kinase contributes to the abnormal distribution of HuR in amyotrophic lateral sclerosis. | LitMetric

Aberrant activation of AMP-activated protein kinase contributes to the abnormal distribution of HuR in amyotrophic lateral sclerosis.

FEBS Lett

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Institute of Neuroscience, National Yang-Ming University, Taipei 112, Taiwan. Electronic address:

Published: February 2015

AI Article Synopsis

Article Abstract

Distorted mRNA metabolism contributes to amyotrophic lateral sclerosis (ALS). The human antigen R (HuR) is a major mRNA stabilizer. We report that abnormal localization of HuR was associated with enhanced AMP-activated protein kinase (AMPK) activity in the motor neurons of ALS patients. Activation of AMPK changed the location of HuR in mouse motor neurons and in a motor neuron cell line via phosphorylation of importin-α1. Stimulation of the A2A adenosine receptor normalized the AMPK-evoked redistribution of HuR. This suggests that aberrant activation of AMPK in motor neurons disrupts the normal distribution of HuR, which might imbalance RNA metabolism and contribute to ALS pathogenesis.

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Source
http://dx.doi.org/10.1016/j.febslet.2014.12.029DOI Listing

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