Increased expression of human antiviral protein MxA in FUS proteinopathy in amyotrophic lateral sclerosis.

FUS mutations are one of the major mutations in familial amyotrophic lateral sclerosis (ALS). The pathological hallmark is FUS-positive neuronal cytoplasmic inclusions (FUS-NCI), known as FUS proteinopathy. Human myxovirus resistance protein 1 (MxA) is an IFN-induced dynamin-like GTPase that acts as antiviral factor. In this study, we examined the expression of MxA in neurons bearing FUS-NCI. We performed immunohistochemistry for FUS and MxA to examine the expression of MxA in two autopsy cases with different FUS gene mutations localized at the nuclear localization signal site (Case 1, H517P; Case 2, R521C). MxA. Most neurons bearing FUS-NCI have increased cytoplasmic MxA expression. Increased cytoplasmic MxA showed several distribution patterns in relation to FUS-NCIs such as the following: colocalization with NCI, distribution more widely than NCI, and different distribution peaks from NCI. Our results suggested that antiviral signaling IFNs are involved upstream in the formation of FUS-NCI in ALS-FUS patients.