The role of autophagy protein Atg5 in multiple sclerosis

Abstract

Multiple sclerosis (MS) is a neurological disease which has a strong autoimmune component to its pathology. Although there are currently many approved immunomodulatory treatments that reduce the rate of relapse and slow down the progression of the disease, the cure is still elusive. This may be due to the underlying etiology still being unknown. Autophagy is the potential link between neurodegeneration and autoimmunity. Specifically, this review will focus on the autophagy protein Atg5 and examine the in vitro cell culture, animal and human studies that have examined its expression and effects in the context of MS. The findings of these investigations are summarized, and a model is proposed in which elevated Atg5 levels leads to dysfunctional autophagy, neurodegeneration, inflammation, and eventually clinical disability. While there are currently no drugs that specifically target Atg5, our review recommends that further investigations into the role that Atg5 plays in MS pathophysiology may eventually lead to the development of autophagy-specific treatments of MS.