Neuromuscular Junction Formation, Aging, and Disorders

Annu Rev Physiol. 2018 Feb 10;80:159-188. doi: 10.1146/annurev-physiol-022516-034255. Epub 2017 Dec 1.


Synapses, the fundamental unit in neuronal circuits, are critical for learning and memory, perception, thinking, and reaction. The neuromuscular junction (NMJ) is a synapse formed between motoneurons and skeletal muscle fibers that is covered by Schwann cells (SCs). It is essential for controlling muscle contraction. NMJ formation requires intimate interactions among motoneurons, muscles, and SCs. Deficits in NMJ formation and maintenance cause neuromuscular disorders, including congenital myasthenic syndrome and myasthenia gravis. NMJ decline occurs in aged animals and may appear before clinical presentation of motoneuron disorders such as amyotrophic lateral sclerosis. We review recent findings in NMJ formation, maintenance, neuromuscular disorders, and aging of the NMJ, focusing on communications among motoneurons, muscles and SCs, and underlying mechanisms.

Keywords: NMJ disorders; Schwann cells; Wnt signaling; agrin-Lrp4-MuSK signaling; neuromuscular junction; retrograde signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Aging / physiology*
  • Animals
  • Humans
  • Motor Neurons / physiology*
  • Muscle Fibers, Skeletal / physiology
  • Neuromuscular Diseases / physiopathology*
  • Neuromuscular Junction / physiology*