Neuromuscular Junction as an Entity of Nerve-Muscle Communication

Abstract

One of the crucial systems severely affected in several neuromuscular diseases is the loss of effective connection between muscle and nerve, leading to a pathological non-communication between the two tissues. The neuromuscular junction (NMJ) represents the critical region at the level of which muscle and nerve communicate. Defects in signal transmission between terminal nerve endings and muscle membrane is a common feature of several physio-pathologic conditions including aging and Amyotrophic Lateral Sclerosis (ALS). Nevertheless, controversy exists on whether pathological events beginning at the NMJ precede or follow loss of motor units. In this review, the role of NMJ in the physio-pathologic interplay between muscle and nerve is discussed.

Keywords: ALS; NMJ; PKC; aging; muscle-nerve interaction.

Figure 1

Amyotrophic Lateral Sclerosis (ALS) and Aging share some common pathologic features. The diagram depicts the relevant pathologic changes observed in ALS and aging.

Figure 2

A summary of the relevant changes, cells, and signaling involved in the pathogenesis of ALS and aging. Morphological and functional alterations of the neuromuscular junction (NMJ) represent part of the earliest signs of aging and ALS. NMJ development, remodelling, and stability is also influenced by different signals and cells, including PSCs and kranocytes. According to the dying back hypothesis, and based on studies regarding how skeletal muscle interventions can influence NMJ, further studies should be encouraged to verify whether combinatorial approaches on different cell and tissue targets induce more satisfactory therapeutic benefits and to define whether a sort of “saving back” approach can be promoted to preserve NMJ integrity, to delay motor neuron impairment, and to counteract muscle-nerve dysfunction.