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ORIGINAL RESEARCH article
Front. Neurol.
Sec. Neurological Biomarkers
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1556120
Muscle-specific kinase levels in blood are an early diagnostic biomarker for SOD1-93A mouse model of ALS
Provisionally accepted- 1Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology, Itabashi, Japan
- 2Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, Itabashi, Japan
- 3Mechanism Aging, Tokyo Metropolitan Institute of Gerontology, Itabashi, Japan
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Neuromuscular junction (NMJ) denervation is an early event preceding motor neuron loss in amyotrophic lateral sclerosis (ALS). Progressive loss of the NMJ leads to irreversible muscle weakness and atrophy. Muscle-specific kinase (MuSK), locally expressed at the postsynaptic membrane of the NMJ, is activated by agrin released from motor nerve terminals and is essential for NMJ maintenance and regeneration. Here, we found that the progression of NMJ denervation prior to the onset of muscle weakness in SOD1-93A mouse model of ALS correlated with increased serum MuSK immunoreactivity and elevated MuSK expression throughout the skeletal muscle. Our results suggest that neuromuscular failure associated with the onset of muscle weakness increases MuSK expression throughout the muscle, which is subsequently cleaved by proteolytic enzymes to increase MuSK immunoreactivity in the blood. These results demonstrate that the level of serum MuSK immunoreactivity may indicate the early phase of NMJ denervation and serve as a biomarker for assessing the progression of other types of ALS and therapeutic benefits in preclinical studies.
Keywords: SOD1 mouse G93A, NMJ, biomarker, Musk, diagnosis, mouse model
Received: 06 Jan 2025; Accepted: 11 Apr 2025.
Copyright: © 2025 Mori, Zhou, Omura, Tsumoto, Miura and Shigemoto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kazuhiro Shigemoto, Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology, Itabashi, Japan
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