“Every breath you take and every move you make…” pulses the opening lyric of a popular rock anthem. Breathing and movement depend on the integrity of neuromuscular junctions.1 These minute unions between motor neurons and muscle fibres were first visualised in vertebrates by Louis Ranvier and by Wilhelm Kühne. Advances in silver staining enabled Jorge Tello, a distinguished pupil of Ramón y Cajal, to analyse neuromuscular junctions in human muscle for the first time.2 Live-imaging microscopy combined with electromyography, albeit limited to experimental animals, now enables their visualisation in situ with micrometre resolution (appendix).3
Neuromuscular paralysis is a hallmark of synaptic neurotoxicity, and characterises autoimmune or congenital myasthenic syndromes, in which either release or sensitivity to acetylcholine is compromised. Organophosphorus poisoning inhibits acetylcholinesterase at the neuromuscular junction and can cause complex excitotoxic pathology, desensitisation of acetylcholine receptors, and even lethal paralysis.4 Wallerian degeneration of axons and neuromuscular junctions is triggered when the continuity between motor neuron cell bodies and their axon terminals is broken, severing the bonds between mind and muscle. Such loss of connectivity occurs in neurodegenerative conditions, including motor neuron diseases, from spinal muscular atrophy to amyotrophic lateral sclerosis. Hence, there is a pressing need to improve our understanding of these mechanisms and to rescue functionally impaired neuromuscular junctions. A recent study showed that the inhibition of Sarm1 in rodent neurons protected axons and neuromuscular junctions from genetically induced degeneration.5 This type of study inspires confidence that motor neuron diseases might soon become a matter only for historians of neuroscience.
Supplementary Material
References
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