Skip to content
DraconiticResearch
Search Sources API
203,948 studies31 sourcesUpdated 11 min ago
Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Neuromuscular Junction Degeneration in Skeletal Muscle Atrophy: Disease-Specific Mechanisms, Evidence-Informed Stratification, and Therapeutic Windows

  • Shiming Li1,2
  • Mengyu Liu1
  • Peng Zhang3
  • Xuemei Ma1
  • Xiaoping Chen2
  1. 1College of Chemistry and Life Sciences, Beijing University of Technology, Beijing 100124, China
  2. 2National Key Laboratory of Human Factors Engineering, China Astronaut Research and Training Center, Beijing 100094, China
  3. 3National Key Laboratory of Space Medicine, China Astronaut Research and Training Center, Beijing 100094, China
Read full textPDFDOICite

Abstract

Skeletal muscle atrophy involves not only the loss of muscle mass and fiber size, but also a significant decline in contractile performance. Force decline often occurs before visible fiber atrophy, suggesting that early defects in neuromuscular transmission might trigger or exacerbate the wasting process. Therefore, we argue that neuromuscular junction (NMJ) degeneration is not a universal, conserved pathway across all atrophy syndromes. Instead, it should be viewed as a stage- and disease-specific event, with its actual contribution varying based on specific evidence. To explore this, we compare NMJ maintenance and degeneration across a broad spectrum of conditions, ranging from primary neuromuscular diseases (like denervation and motor neuron disorders) to systemic states such as aging, cachexia, and metabolic or respiratory diseases. Based on this, we propose a framework to evaluate NMJ involvement by timing, lesion type, and reversibility, drawing on diverse evidence from morphological, electrophysiological, and biomarker studies. Crucially, this approach distinguishes primary synaptic disorders from systemic conditions where NMJ damage acts merely as a secondary modifier. Ultimately, aligning specific molecular lesions with practical intervention windows will help refine patient stratification and guide the design of more targeted NMJ therapies.

Related

  1. The m6A methyltransferase METTL3 in intervertebral disc degeneration: from molecular mechanisms to therapeutic potential
    Yi-Chun Zhou, Xiang-Song Xiang, Geng Li +2
    Frontiers in cell and developmental biologyPeer-reviewedCC BYFull textGeneral biochemistryEurope PMC
  2. SH3BP2 deficiency in skeletal muscle leads to neuromuscular junction abnormalities and decreased muscle strength.
    Bhola Shankar Pradhan, Krzysztof M Bernadzki, Yauhen Bandaruk +9
    Frontiers in molecular neurosciencePeer-reviewedCC BYFull textMolecular biology & gene regulationEurope PMC
  3. Rapsyn overexpression improves neuromuscular junction and skeletal muscle function after tourniquet-induced mouse hindlimb ischemia-reperfusion injuries
    Huiyin Tu, Emmanuel Adu-Agyekum, Aaron N. Barksdale +2
    Frontiers in bioengineering and biotechnologyPeer-reviewedCC BYFull textMolecular biology & gene regulationEurope PMCEurope PMCPMC
  4. Exploring clinically anchored therapeutic stratification and tumor-stroma heterogeneity using patient-derived 3D bioprinted primary liver cancer models.
    Kai Zhang, Liwei Du, Minghao Sun +16
    Molecular cancerPeer-reviewedCC BY-NC-NDFull textGeneral biochemistryEurope PMC
  5. Organelle-specific mechanisms and AI-guided stratification in gut-renal-vascular axis modulation
    Jin Chen, Xuebin Cao, Shihong Xiong +9
    Clinical EpigeneticsPeer-reviewedCC BY-NC-ND 4.0Full textMolecular biology & gene regulationPMC

Cite

BibTeXRIS
BibTeX
@article{li2026neuromuscular,
  title = {{Neuromuscular Junction Degeneration in Skeletal Muscle Atrophy: Disease-Specific Mechanisms, Evidence-Informed Stratification, and Therapeutic Windows}},
  author = {Shiming Li and Mengyu Liu and Peng Zhang and Xuemei Ma and Xiaoping Chen},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27209264},
  url = {https://www.mdpi.com/1422-0067/27/20/9264},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Neuromuscular Junction Degeneration in Skeletal Muscle Atrophy: Disease-Specific Mechanisms, Evidence-Informed Stratification, and Therapeutic Windows
AU  - Shiming Li
AU  - Mengyu Liu
AU  - Peng Zhang
AU  - Xuemei Ma
AU  - Xiaoping Chen
PY  - 2026
DA  - 2026/10/19
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27209264
UR  - https://www.mdpi.com/1422-0067/27/20/9264
AB  - Skeletal muscle atrophy involves not only the loss of muscle mass and fiber size, but also a significant decline in contractile performance. Force decline often occurs before visible fiber atrophy, suggesting that early defects in neuromuscular transmission might trigger or exacerbate the wasting process. Therefore, we argue that neuromuscular junction (NMJ) degeneration is not a universal, conserved pathway across all atrophy syndromes. Instead, it should be viewed as a stage- and disease-specific event, with its actual contribution varying based on specific evidence. To explore this, we compare NMJ maintenance and degeneration across a broad spectrum of conditions, ranging from primary neuromuscular diseases (like denervation and motor neuron disorders) to systemic states such as aging, cachexia, and metabolic or respiratory diseases. Based on this, we propose a framework to evaluate NMJ involvement by timing, lesion type, and reversibility, drawing on diverse evidence from morphological, electrophysiological, and biomarker studies. Crucially, this approach distinguishes primary synaptic disorders from systemic conditions where NMJ damage acts merely as a secondary modifier. Ultimately, aligning specific molecular lesions with practical intervention windows will help refine patient stratification and guide the design of more targeted NMJ therapies.
SN  - 1422-0067
ER  -