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AMPK regulates the maintenance and remodelling of the neuromuscular junction. | LitMetric

AI Article Synopsis

  • This study investigates the role of AMP-activated protein kinase (AMPK) in maintaining and adapting the neuromuscular junction (NMJ), which is crucial for muscle function.
  • Researchers used various methods to analyze how AMPK in skeletal muscle affects the NMJ and identified that it is more abundant in younger mice but decreases with age.
  • The results suggest that AMPK is vital for NMJ stability and adaptability, making it a promising target for treating age-related and neuromuscular disorders.

Article Abstract

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.

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Source
http://dx.doi.org/10.1016/j.molmet.2024.102066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646796PMC

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