Intravenous immunoglobulin ameliorates motor and cognitive deficits and neuropathology in R6/2 mouse model of Huntington's disease by decreasing mutant huntingtin protein level and normalizing NF-κB signaling pathway

Abstract

Huntington's disease (HD) is a fatal neurodegenerative disorder characterized by progressive movement disorders and cognitive deficits, which is caused by a CAG-repeat expansion encoding an extended polyglutamine (polyQ) tract in the huntingtin protein (HTT). Reduction of mutant HTT levels and inhibition of neuroinflammation has been proposed as a major therapeutic strategy in treating HD. Intravenous immunoglobulin (IVIg) therapy has been firmly established for the treatment of several autoimmune or inflammatory neurological diseases, either as adjunctive treatment or as first-line therapy. However, whether IVIg has therapeutic potential on HD remains unclear. Here we for the first time demonstrated that IVIg treatment remarkably rescued motor and cognitive deficits, prevented synaptic degeneration, attenuated neuroinflammation and oxidative stress in R6/2 mouse model. Further investigation showed that the beneficial effects of IVIg resulted from the reduced levels of mutant HTT and inhibition of NF-κB signalling pathway. These findings suggest that IVIg is a promising therapeutic potential for HD.

Keywords: Huntingtin protein; Huntington’s disease; Intravenous immunoglobulin; Polyglutamine.