Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron (MN) degeneration leading to its death. While the cause of MN death is unknown, one hypothesis is that its cellular environment may play a key role in its survival. However, in ALS, circulating extracellular vesicles that can transport toxic elements to the astrocytes are observed, and the muscle is an excretor of vesicles.
Based on muscle biopsies from patients with sporadic ALS and the analysis of secreted muscle vesicles, the authors observe:
- the accumulation of multivesicular bodies in the biopsies, on healthy myotubes,
- ALS vesicles induce shortened and less branched neurites, cell death and disrupted localization of RNA and RNA processing proteins,
- the toxicity of the FUS protein according to its level of expression in the receptor proteins,
- the abolition of toxicity for recipient NMs by immunoblocking vesicle uptake.
The results show that ALS muscle vesicles transport proteins toxic to MNs. The authors infer that skeletal muscle is a potential source of vesicle-mediated toxicity in ALS.
