Changes of Sonic Hedgehog mediated FAK/ERK pathway proteins in amyotrophic lateral sclerosis model mice.

Sonic Hedgehog (SHH) has been shown to be cytoprotective against oxidative stress in a cellular model of amyotrophic lateral sclerosis, and it may support the proliferation and differentiation of endogenous stem cells along the motor neuron lineage and stimulate motor neuron growth and axon formation. However, there is less validation of the role of SHH in a mouse model of amyotrophic lateral sclerosis(ALS). In hSOD1G93A transgenic mice, 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 from Western Blot and immunohistochemistry. And compared to the hSOD1 control group, the SHH, FAK, ERK, p-FAK, p-ERK protein levels increased by stimulating SHH with an agonist, while SHH, FAK, p-FAK protein decreased significantly by inhibiting SHH. And the HE staining results of mouse gastrocnemius muscle showed that the agonist group had an increased muscle morphology and more muscle fibers, while the inhibitor group had an atrophied muscle morphology and fewer muscle fibers, than the hSOD1 control group. This confirmed the upstream-downstream relationship among SHH, FAK, and ERK in the spinal cord tissues of hSOD1 mice. Western blot analysis of ERK and p-ERK and immunohistochemical staining revealed declining ERK protein expression in hSOD1 mice, which progressively decreased over time. PUR increased ERK expression, whereas CYC had no significant effect on its reduction. So 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.