Muscle Fibers Secrete FGFBP1 to Slow Degeneration of Neuromuscular Synapses during Aging and Progression of ALS.

Abstract

The neuromuscular junction (NMJ) is critical for all voluntary movement. Its malformation during development and degeneration in adulthood impairs motor function. Therefore, it is important to identify factors that function to maintain the structural integrity of NMJs. We show that muscle fibers secrete and concentrate the fibroblast growth factor binding protein 1 (FGFBP1) at NMJs. However, FGFBP1 expression decreases in skeletal muscles during aging and before NMJ degeneration in SOD1G93A mice, a mouse model for amyotrophic lateral sclerosis. We show that transforming growth factor-β1 is responsible for the decreased levels of FGFBP1. Importantly, we demonstrate critical roles for FGFBP1 at NMJs in developing, aging and SOD1G93A mice.