Titolo della tesi: “MOLECULAR AND CELLULAR NETWORKS DRIVING NEUROGENIC MUSCLE ATROPHY”
During neurogenic muscle atrophy, the interruption of transmission of neurogenic signals to muscles, caused by loss of neuromuscular junction (NMJ) integrity, leads to muscle atrophy, an event that causes loss of muscle functionality with the obvious deleterious outcomes. NMJs degeneration is a prominent aspect of denervation, aging, and some pathological conditions, such as Amyotrophic Lateral Sclerosis (ALS). The precise molecular mechanisms and roles of muscle-resident cells, during neurogenic muscle atrophy, remain largely unknown. Evidence suggests that the effect on myofibers caused by neuron loss involves neighboring resident cells. Therefore, we analyzed the gene expression profiles at bulk and single-cell level of Itga7-expressing cells in muscle and revealed the existence of a subpopulation of muscle-resident glial cells, distinct from muscle satellite cells, that is selectively activated upon nerve injury. Upon nerve lesion, these cells expand and activate a neurotrophic program, that is turn off upon recovery of NMJ integrity. Moreover, these muscle-resident glial cells in the ALS mouse model increase during disease progression but exhibit impaired neurotrophic activity, suggesting that defective activation of glial cells could be implicated in ALS pathogenesis. Therefore, a better understanding of the cellular and molecular signaling pathways in muscle-resident cells during traumatic or pathological denervation is critical for developing better therapies against neurogenic muscle atrophy and degenerative diseases such as ALS.