A study by an international group of researchers in Israel, the U.S., and Germany indicates that type I interferon may contribute to Gaucher disease, specifically in a subset characterized by neuroinflammation. The report, “Induction of the type I interferon response in neurological forms of Gaucher disease,“ appeared in the Journal of Neuroinflammation.
Interferons are proteins that help to regulate the immune system. In some cases, interferons may be elevated at abnormal levels, contributing to disease.
In Gaucher disease, glucocerebroside, which is a type of fatty substance, accumulates in cells and does not get broken down by lysosomes (a lysosome is a cellular region that breaks down molecules). People with Gaucher’s disease consequently have fatigue, bruising, anemia, and enlarged organs, among other symptoms. The disease is caused by mutations in the GBA1 gene and is considered a significant risk factor for Parkinson’s. Neuroinflammation is found in some forms of Gaucher disease.
Investigators, led by Einat B. Vitner with the Department of Biomolecular Sciences, Weizmann Institute of Science, in Rehovot, Israel, studied a mouse model of Gaucher disease that lacks an enzyme needed to break down glucocerebroside. They used what is known as an unbiased gene profile analysis to identify genes that increase in the nervous systems of the animals.
Results showed that 10 genes involved in high immune system responses (inflammation) increased in a brain region known as the thalamus. Overall, the researchers found that interferon β levels increased in neurons, while genes known to be stimulated by interferons increased in microglia. Microglia are nervous system cells that control immune system responses to injury, infections, and toxins.
When type I interferon was blocked from cellular signaling via its receptor, this reduced expression of the immune system-related genes but did not affect the animals’ health.
“Our results imply that the type I interferon response is involved in the development of [neuroinflammation-related Gaucher disease] pathology, and possibly in other lysosomal storage diseases in which simple glycosphingolipids accumulate, and support the notion that interferon signaling pathways play a vital role in the sterile inflammation that often occurs during chronic neurodegenerative diseases in which neuroinflammation is present,” the investigators concluded.
Overall, this study implicates type I interferon in Gaucher disease and suggests that it could be a good target for treatments, specifically in those individuals with neuroinflammation. However, further research is needed in people to confirm this association.
