Beta-2 microglobulin is important for disease progression in a murine model for amyotrophic lateral sclerosis

Beta-2 microglobulin (beta 2m) is an essential component of the major histocompatibility complex (MHC) class I proteins and in the nervous system beta 2m is predominantly expressed in motor neurons. As beta 2m can promote nerve regeneration, we investigated its potential role in amyotrophic lateral sclerosis (ALS) by investigating its expression level as well as the effect of genetically removing beta 2m on the disease process in mutant superoxide dismutase 1 (SOD1(G93A)) mice, a model of ALS. We observed a strong upregulation of beta 2m in motor neurons during the disease process and ubiquitous removal of beta 2m dramatically shortens the disease duration indicating that beta 2m plays an essential and positive role during the disease process. We hypothesize that beta 2m contributes to plasticity that is essential for muscle reinnervation. Absence of this plasticity will lead to faster muscle denervation and counteracting this process could be a relevant therapeutic target.