Pharmacological effects of denervated muscle atrophy due to metabolic imbalance in different periods

Denervation-induced skeletal muscle atrophy can potentially cause the decline in the quality of life of patients and an increased risk of mortality. Complex pathophysiological mechanisms with dynamic alterations have been documented in skeletal muscle atrophy resulting from innervation loss. Hence, an in-depth comprehension of the key mechanisms and molecules governing skeletal muscle atrophy at varying stages, along with targeted treatment and protection, becomes essential for effective atrophy management. Our preliminary research categorizes the skeletal muscle atrophy process into four stages using microarray analysis. This review extensively discusses the pathways and molecules potentially implicated in regulating the four stages of denervation and muscle atrophy. Notably, drugs targeting the reactivare oxygen species stage and the inflammation stage assume critical roles. Timely intervention during the initial atrophy stages can expedite protection against skeletal muscle atrophy. Additionally, pharmaceutical intervention in the ubiquitin-proteasome pathway associated with atrophy and autophagy lysosomes can effectively slow down skeletal muscle atrophy. Key molecules within this stage encompass MuRF1, MAFbx, LC3II, p62/SQSTM1, etc. This review also compiles a profile of drugs with protective effects against skeletal muscle atrophy at distinct post-denervation stages, thereby augmenting the evidence base for denervation-induced skeletal muscle atrophy treatment.