期刊
FEBS LETTERS
卷 589, 期 4, 页码 432-439出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2014.12.029
关键词
A(2A) adenosine receptor; AMP-activated protein kinase; Amyotrophic lateral sclerosis; cAMP; Human antigen R; Importin-alpha 1
资金
- National Science Council [NSC 100-2325-B001-003, NSC 101-2325-B-001-003, NSC 102-2325-B-001-003]
- Institute of Biomedical Sciences of Academia Sinica
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-alpha 1. 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. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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