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

ABSTRACT

Beta-2 microglobulin (ß2m) is an essential component of the major histocompatibility complex (MHC) class I proteins and in the nervous system ß2m is predominantly expressed in motor neurons. As ß2m 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 ß2m on the disease process in mutant superoxide dismutase 1 (SOD1 (G93A) ) mice, a model of ALS. We observed a strong upregulation of ß2m in motor neurons during the disease process and ubiquitous removal of ß2m dramatically shortens the disease duration indicating that ß2m plays an essential and positive role during the disease process. We hypothesize that ß2m 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.