Abstract
Spinal alpha-motoneurons are classified in several types depending on the contractile properties of the innervated muscle fibers. This diversity is further displayed in different levels of vulnerability of distinct motor units to neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS). We summarize recent data suggesting that, contrary to the excitotoxicity hypothesis, the most vulnerable motor units are hypoexcitable and experience a reduction in their firing prior to symptoms onset in ALS. We suggest that a dysregulation of activity-dependent transcriptional programs in these motoneurons alter crucial cellular functions such as mitochondrial biogenesis, autophagy, axonal sprouting capability and re-innervation of neuromuscular junctions.
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Acknowledgments
MB is supported by National Science Centre 2017/26/D/NZ7/00728. MM and DZ are supported by NIH-NINDS R01NS110953, the Thierry Latran Foundation project “TRiALS”, Association pour la Recherche sur la SLA et autres maladies du motoneurone (ARSLA), the Association Française contre les Myopathies (AFM) project “HYPERTOXIC”, Radala Foundation for ALS Research, and Programme Hubert Curien “Polonium” for scientific exchanges. MM would like to thank Alexandra Elbakyan for her help with bibliography. FR is supported by the Thierry Latran Foundation (projects “Trials” and “Hypothals”), by the Radala Foundation, by the Deutsche Forschungsgemeinschaft (DFG) as part of the SFB1149 and with the individual grant no. 431995586 (RO-5004/8-1) and no. 443642953 (RO5004/9-1), by the Cellular and Molecular Mechanisms in Aging (CEMMA) Research Training Group and by BMBF (FKZ 01EW1705A, as member of the ERANET-NEURON consortium “MICRONET”). Clipart in Fig. 6 are adapted from Servier Medical Art by Servier, licensed under a Creative Commons Attribution 3.0 Unported License.
The authors declare no conflict of interest.
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Bączyk, M., Manuel, M., Roselli, F., Zytnicki, D. (2022). From Physiological Properties to Selective Vulnerability of Motor Units in Amyotrophic Lateral Sclerosis. In: O'Donovan, M.J., Falgairolle, M. (eds) Vertebrate Motoneurons. Advances in Neurobiology, vol 28. Springer, Cham. https://doi.org/10.1007/978-3-031-07167-6_15
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