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Aberrant activation of AMP‐activated protein kinase contributes to the abnormal distribution of HuR in amyotrophic lateral sclerosis
Author(s) -
Liu Yu-Ju,
Lee Li-Ming,
Lai Hsing-Lin,
Chern Yijuang
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.12.029
Subject(s) - ampk , amyotrophic lateral sclerosis , protein kinase a , motor neuron , amp activated protein kinase , phosphorylation , kinase , rna binding protein , chemistry , microbiology and biotechnology , messenger rna , biology , neuroscience , medicine , biochemistry , gene , disease , spinal cord
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 A 2A 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.