Abnormal regulation of the antiviral response in neurological/neurodegenerative diseases

Abstract

Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis are a few examples of debilitating neurological/neurodegenerative diseases for which there are currently no curative treatments. Recent evidence has strongly suggested a role for neuroinflammation in both the onset and progression of these diseases. However, the mechanisms that initiate neuroinflammation are presently unclear. Mounting evidence suggests that environmental factors are likely involved. One proposed mechanism linking both genetic and environmental factors is dysregulation of the antiviral response. Indeed, many mutations that have been linked to neurological conditions occur in genes related to the antiviral response. Although the products of these genes may have potent antiviral activities - they can also have deleterious effects when their expression is not appropriately regulated. For that reason, expression of antiviral genes is a tightly controlled process. Herein, we review the various antiviral genes that have been linked to neurological conditions. We focus specifically on type I interferonopathies, the symptoms of which are often evident at birth, and neurodegenerative diseases, which frequently onset later in life.

Keywords: Amyotrophic lateral schlerosis; Innate immunity; Neurodegenerative diseases; Type I interferonopathies; Viruses.