Study on the pathogenesis of hSOD1 mice by SHH through FAK/ERK pathway

Abstract

AbstractAmyotrophic lateral sclerosis (ALS) is an irreversible neurodegenerative disease that involves the spinal cord and then causes reduced function of the extremities, and eventually often involves respiratory muscles and leads to death, 10% of cases are related to family inheritance, and the most frequent gene mutation is SOD1. In hSOD1G93A transgenic mice using Western Blot and immunohistochemistry techniques we found that the expression of SHH, FAK, ERK, p-FAK, and p-ERK was progressively decreased in the spinal cord tissue of hSOD1 mice over time. By stimulating SHH with an agonist, the SHH, FAK, ERK, p-FAK, p-ERK protein levels increased, while SHH, FAK, p-FAK protein decreased significantly by inhibiting SHH compared to the hSOD1 control group. The HE staining results of mouse gastrocnemius muscle showed that the agonist group had an increased muscle morphology and more muscle fibers than the hSOD1 control group, while the inhibitor group had an atrophied muscle morphology and fewer muscle fibers than the hSOD1 control group. Our experiments confirmed that SHH, FAK and ERK may have an upstream and downstream relationship in the spinal cord tissue of hSOD1 mice, and that PUR can activate SHH protein and enhance the function of FAK/ERK. SHH is suggested to play a protective role in the muscle tissue of hSOD1 mice through the FAK/ERK pathway.