Cover Story Current Issue
Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges due to its hidden onset, high malignancy, and the lack of effective treatments. Together with surgery, adjuvant or neoadjuvant chemotherapy remains the primary treatment for patients with resectable or borderline resectable disease. However, the extensive metabolic reprogramming exhibited by pancreatic cancer cells interacts with oncogenes to affect the expression of key enzymes and signaling pathways, resulting in limited response to therapy and chemoresistance.
Current Issue
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, 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.
Articles in Press
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, 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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12th Helmholtz
Diabetes Conference
22-24. Sep, Munich
You are what you eat
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