Neuromuscular junction innervation and motor function are preserved by restoring muscarinic signaling in perisynaptic glia in ALS.
Overview
- Université de Montréal, Département de Neurosciences, Montréal, QC, Canada
- Centre Interdisciplinaire de Recherche sur le Cerveau et l’Apprentissage (CIRCA), Montréal, QC, Canada
- Groupe de recherche sur la signalisation neurale et la circuiterie (GRSNC), Montréal, QC, Canada
- Institut Courtois d’innovation biomédicale, Faculté de médecine, Université de Montréal, Montréal, QC, Canada
- Université de Montréal, Faculté de l’apprentissage continu, Montréal, QC, Canada
Abstract
Neuromuscular junction (NMJ) denervation is an early pathological event in amyotrophic lateral sclerosis (ALS) causing motor dysfunction and paralysis. Glial cells at the NMJ, perisynaptic Schwann cells (PSCs), ensure a balance between maintenance and repair via muscarinic receptor signaling. However, in ALS mouse models, PSCs show an aberrant muscarinic hyperactivation. We posited that this excessive activation impairs the PSC capacity to support NMJ repair in ALS. Beginning at symptoms onset, SOD1G37R mice received daily oral administration of darifenacin, a clinically approved type 3 muscarinic receptor antagonist, to reduce PSC hyperactivation. The treatment improved locomotion and preserved NMJ innervation in male mice, with comparable effects observed in females, and extended survival in males. Functional benefits were supported by signs of glial repair and enhanced survival of lumbar motor neurons. These preclinical data indicate that pathological PSC hyperactivity contributes to NMJ denervation in ALS and support therapeutic strategies targeting NMJs in ALS.
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
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Data
Datasets cited
- doi:10.17632/
2h29gjfmyp.1 , at the source; found in “Data and code availability” - doi:10.17632/
4csgm6z25y.1 , at the source; found in “Data and code availability” - doi:10.17632/
kzmcprftmr.1 , at the source; found in “Data and code availability” - doi:10.17632/
nkrwysnzj6.1 , at the source; found in “Data and code availability” - doi:10.17632/
tj888d7mt7.1 , at the source; found in “Data and code availability”
Data and code availability
All data reported in this study is deposited in the online repository at: Mendeley data: https://
This paper does not report original code.
Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Versions
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Version 1, 29 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 4 keywords, 1 funder, 78 references, 18 RRIDs.
Cite
This paper
Tremblay, E., Arbour, D., Vallée, J., Piovesana, R., Vallières, G., Mechichi, E., & Robitaille, R. (2026). Neuromuscular junction innervation and motor function are preserved by restoring muscarinic signaling in perisynaptic glia in ALS. iScience, 29(5), 115565. https://
BibTeX
@article{tremblay2026neu
author = {Tremblay, Elsa and Arbour, Danielle and Vallée, Joanne and Piovesana, Roberta and Vallières, Geneviève and Mechichi, Emine and Robitaille, Richard},
title = {{Neuromuscular junction innervation and motor function are preserved by restoring muscarinic signaling in perisynaptic glia in ALS}},
journal = {iScience},
year = {2026},
month = apr,
volume = {29},
number = {5},
pages = {115565},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/
url = {https://
pmid = {42095090},
pmcid = {PMC13141810}
}
RIS
TY - JOUR
AU - Tremblay, Elsa
AU - Arbour, Danielle
AU - Vallée, Joanne
AU - Piovesana, Roberta
AU - Vallières, Geneviève
AU - Mechichi, Emine
AU - Robitaille, Richard
TI - Neuromuscular junction innervation and motor function are preserved by restoring muscarinic signaling in perisynaptic glia in ALS
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/
VL - 29
IS - 5
SP - 115565
SN - 2589-0042
PB - Elsevier
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
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"language": "en",
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