Harnessing Immunoproteostasis to Treat Neurodegenerative Disorders

Abstract

Immunoproteostasis is a term used to reflect interactions between the immune system and the proteinopathies that are presumptive "triggers" of many neurodegenerative disorders. The study of immunoproteostasis is bolstered by several observations. Mutations or rare variants in genes expressed in microglial cells, known to regulate immune functions, or both can cause, or alter risk for, various neurodegenerative disorders. Additionally, genetic association studies identify numerous loci harboring genes that encode proteins of known immune function that alter risk of developing Alzheimer's disease (AD) and other neurodegenerative proteinopathies. Further, preclinical studies reveal beneficial effects and liabilities of manipulating immune pathways in various neurodegenerative disease models. Although there are concerns that manipulation of the immune system may cause more harm than good, there is considerable interest in developing immune modulatory therapies for neurodegenerative disorders. Herein, I highlight the promise and challenges of harnessing immunoproteostasis to treat neurodegenerative proteinopathies.

Keywords: genetic risk; immune system; immunoproteostasis; neurodegenerative disease; therapeutics.