Skeletal muscle atrophy after sciatic nerve damage: Mechanistic insights

Abstract

Sciatic nerve injury leads to molecular events that cause muscular dysfunction advancement in atrophic conditions. Nerve damage renders muscles permanently relaxed which elevates intracellular resting Ca²⁺ levels. Increased Ca²⁺ levels are associated with several cellular signaling pathways including AMPK, cGMP, PLC-β, CERB, and calcineurin. Also, multiple enzymes involved in the tricarboxylic acid cycle and oxidative phosphorylation are activated by Ca²⁺ influx into mitochondria during muscle contraction, to meet increased ATP demand. Nerve damage induces mitophagy and skeletal muscle atrophy through increased sensitivity to Ca²⁺-induced opening of the permeability transition pore (PTP) in mitochondria attributed to Ca²⁺, ROS, and AMPK overload in muscle. Activated AMPK interacts negatively with Akt/mTOR is a highly prevalent and well-described central pathway for anabolic processes. Over the decade several reports indicate abnormal behavior of signaling machinery involved in denervation-induced muscle loss but end up with some controversial outcomes. Therefore, understanding how the synthesis and inhibitory stimuli interact with cellular signaling to control muscle mass and morphology may lead to new pharmacological insights toward understanding the underlying mechanism of muscle loss after sciatic nerve damage. Hence, the present review summarizes the existing literature on denervation-induced muscle atrophy to evaluate the regulation and expression of differential regulators during sciatic damage.

Keywords: Ca(2+) overload; Mitophagy; Muscle atrophy; Reactive oxygen species; Sciatic nerve injury.