AMPK regulates the maintenance and remodelling of the neuromuscular junction

AMPK regulates the maintenance and remodelling of the neuromuscular junction

Objective: The molecular mechanisms underlying the maintenance and adaptability of the neuromuscular junction (NMJ) remain poorly understood. This study aimed to investigate the role of AMP-activated protein kinase (AMPK) as a key regulator of NMJ stability and plasticity. Method: A comprehensive, m...

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Main Authors: Sean Y. Ng, Andrew I. Mikhail, Stephanie R. Mattina, Salah A. Mohammed, Shahzeb K. Khan, Eric M. Desjardins, Changhyun Lim, Stuart M. Phillips, Gregory R. Steinberg, Vladimir Ljubicic
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Molecular Metabolism
Subjects:
Mitochondria
Exercise
Aging
PGC-1α
Acetylcholine receptors
Online Access:http://www.sciencedirect.com/science/article/pii/S2212877824001972
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Summary:Objective: The molecular mechanisms underlying the maintenance and adaptability of the neuromuscular junction (NMJ) remain poorly understood. This study aimed to investigate the role of AMP-activated protein kinase (AMPK) as a key regulator of NMJ stability and plasticity. Method: A comprehensive, multifaceted approach was employed, integrating genetic, physiological, and pharmacological methodologies to elucidate the role of skeletal muscle AMPK in modulating the neuromuscular synapse. Results: Our findings reveal an increased abundance of AMPK transcripts within the NMJ and an age-associated decline in AMPK activity and synapse-specific mitochondrial gene expression. Young mice null for skeletal muscle AMPK displayed a neuromuscular phenotype akin to aged animals. Pharmacological AMPK stimulation facilitated its localization in subsynaptic myonuclei, preceded the induction of several NMJ-related transcripts, and enhanced myotube acetylcholine receptor clustering. Exercise-induced AMPK activation in mouse muscle elicited a broad NMJ-related gene response, consistent with human exercise data. Conclusions: These findings highlight a critical role for AMPK in the maintenance and remodeling of the NMJ, highlighting its potential as a therapeutic target for age-related and neuromuscular disorders.
ISSN:2212-8778

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