Researchers at Florida International University and Columbia University may have found a novel function for translocator protein 18 kDa (TSPO), a widely used biomarker of brain inflammation and injury, which is likely to prove beneﬁcial for the development of therapeutic strategies to mitigate brain injury and neuroinﬂammation.
A team of researchers led by Dr. Tomás R. Guilarte, dean of the Robert Stempel College of Public Health & Social Work, has published the paper, TSPO Finds NOX2 in Microglia for Redox Homeostasis, which identifies a novel function of TSPO in microglia. Dr. Guilarte, along with Columbia University doctoral student, Ms. Meredith K. Loth and research associate, Dr. Sara R. Guariglia, propose that a TSPO interaction with NADPH oxidase (NOX2) links the generation of reactive oxygen species (ROS) to the induction of an antioxidant response to maintain redox homeostasis.
[TSPO levels can help provide a real-time picture of inflammation related to neurodegenerative diseases, which will eventually allow doctors to track how treatment reduces inflammation. Dr. Tomás R. Guilarte, Dr. Meredith K. Loth, Dr. Sara R. Guariglia / Trends in Pharmacological Sciences 2016]
The paper goes on to suggest that the proteins which TSPO interacts with and regulates may differ depending on the glial cell type in which it is expressed. So, TSPO in microglia may have a protective role from the cell-autonomous generation of ROS and other toxic products that activated microglia generate as a result of brain injury. Therefore, it is possible that when microglia are chronically activated — as often occurs in neurodegenerative diseases — the balance of the TSPO – NOX interaction breaks down and the defense mechanisms are no longer able to regulate the level of ROS production. This would result in a chronic “toxic state” in which microglia-induced ROS exceeds antioxidant defenses, resulting in injury not only to microglia, but also to surrounding neurons, thereby causing neurodegeneration.
“This new line of investigation will provide a greater understanding of TSPO glial cell biology, and the knowledge gained may prove beneﬁcial in devising therapeutic strategies for neurodegenerative diseases such as Parkinson’s, multiple sclerosis and Alzheimer’s disease,” said Dr. Guilarte.
Read the full article, TSPO Finds NOX2 in Microglia for Redox Homeostasis in the latest issue of Trends in Pharmacological Sciences.