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Updated: Jan 22, 2026

Tibial Nerve Transection - A Standardized Model for Denervation-induced Skeletal Muscle Atrophy in Mice
10:50

Tibial Nerve Transection - A Standardized Model for Denervation-induced Skeletal Muscle Atrophy in Mice

Published on: November 3, 2013

25.3K

mTORC1 and PKB/Akt control the muscle response to denervation by regulating autophagy and HDAC4

Perrine Castets1, Nathalie Rion2, Marine Théodore2,3

  • 1Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056, Basel, Switzerland. perrine.castets@unibas.ch.

Nature Communications
|July 20, 2019
PubMed

Insights

This study reveals that protein kinase B/Akt and the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway are crucial for maintaining skeletal muscle health and neuromuscular junctions after nerve injury, impacting muscle disease progression.

Area of Science:

  • Muscle biology
  • Neuroscience
  • Cell signaling

Background:

  • Skeletal muscle denervation is a key factor in muscle diseases.
  • The molecular pathways governing muscle response to denervation are not fully understood.

Purpose of the Study:

  • To investigate the roles of protein kinase B/Akt and mechanistic target of rapamycin complex 1 (mTORC1) signaling in muscle homeostasis and neuromuscular junction maintenance following nerve injury.
  • To elucidate the signaling mechanisms underlying the muscle's response to denervation.

Main Methods:

  • Utilized molecular biology techniques to study signaling pathways in denervated skeletal muscle.
  • Investigated the impact of modulating PKB/Akt and mTORC1 activity on autophagy, muscle homeostasis, and neuromuscular endplate integrity.
  • Examined the role of PKB/Akt in regulating HDAC4 nuclear import and gene expression.

Main Results:

  • PKB/Akt and mTORC1 signaling are vital for muscle homeostasis and neuromuscular endplate maintenance after nerve injury.
  • Balanced mTORC1 activation is essential for regulating autophagy and homeostasis in denervated muscle.
  • Sustained mTORC1 activation leads to PKB/Akt inhibition, disrupting synaptic remodeling and causing neuromuscular endplate degeneration.
  • PKB/Akt activation promotes HDAC4 nuclear import, facilitating epigenetic changes and synaptic gene upregulation.

Conclusions:

  • PKB/Akt-mTORC1 signaling plays previously unrecognized roles in the muscle's response to nerve injury.
  • These findings have significant implications for understanding and potentially treating conditions affecting neuromuscular integrity.

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