Fig. 2
From: TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis
Dysfunction of non-neuronal components of the tripartite synapse may impact NMJ integrity in ALS. In the healthy skeletal muscle (left), TDP-43 promotes muscle regeneration and NMJ formation. In ALS (right), TDP-43 dysregulation impairs the expression genes encoding NMJ maintenance proteins (e.g., Dlg, Bet1L) as well as key microRNAs (e.g., miR-1, miR-206, miR2826-p), which may lead to denervation via the disorganization of presynaptic membranes and the release of destabilizing factors (e.g., SEMA3s). In addition to MN presynaptic terminals and muscle endplates, TSCs are the third cellular component of the tripartite synapse. TSC dysfunction (e.g., impairment in synaptic decoding and morphological abnormalities) may impact the ability to maintain NMJ integrity and promote reinnervation