title: Aberrant activation of AMP-activated protein kinase contributes to the abnormal distribution of HuR in amyotrophic lateral sclerosis.
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.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Lee
authors.affiliation: Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Hsing-Lin
authors.initials: HL
authors.lastname: Lai
authors.affiliation: 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: bmychern@ibms.sinica.edu.tw.
authors.forename: Yijuang
authors.initials: Y
authors.lastname: Chern
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D002460:Cell Line; D051959:ELAV Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009046:Motor Neurons / Q000201:enzymology*; D009928:Organ Specificity
chemical_list: D051959:ELAV Proteins; D055372:AMP-Activated Protein Kinases
keywords: A(2A) adenosine receptor; AMP-activated protein kinase; Amyotrophic lateral sclerosis; Human antigen R; Importin-α1; cAMP