Guilarte discovery opens door to further research into treatment of neurodegenerative disease

New paper explains how TSPO levels can help to provide a real-time picture of inflammation related to neurodegenerative diseases

Tomás R. Guilarte, Dean of the Robert Stempel College of Public Health & Social Work, has made a discovery that could potentially help put off or prevent the onset of debilitating diseases such as Parkinson's, multiple sclerosis and Alzheimer's.

The discovery follows a previous study in which his research team first described an association between translocator protein 18kDa — or TSPO — a neuroinflammation protein marker, and NADPH oxidase (NOX)-derived reactive oxygen species (ROS) signalling in microglia. His newest publication proposes a mechanism through which the TSPO-NOX interaction ROS signals to maintain redox homeostasis in microglia.

'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,' said Guilarte, who led the recent research with Columbia University doctoral student Meredith K. Loth and research associate Sara R. Guariglia.

The team's findings have been published in the paper, TSPO Finds NOX2 in Microglia for Redox Homeostasis, which appears in the latest issue of the scientific journal Trends in Pharmacological Sciences. In it, the researchers suggest that TSPO may serve a protective role within cells by defending against the toxic ROS that are generated by microglia as a result of brain injury. It's possible that at a certain point, however, TSPO levels can no longer regulate ROS, resulting in a chronic 'toxic state' that leads to neurodegeneration.

The paper goes on to explain how TSPO levels can help to provide a real-time picture of inflammation related to neurodegenerative diseases, which will eventually allow doctors to track how treatment reduces inflammation.

Currently, for example, the diagnosis of Alzheimer's relies largely on documenting mental decline, such as forgetfulness and a decreased ability to maintain focus and solve problems. But the ability to visualise and measure TSPO levels in the living brain using non-invasive neuroimaging techniques can provide a virtual window to identify and treat Alzheimer's as well as other diseases linked to neuroinflammation.

TSPO levels allow researchers to see a real-time picture of where inflammation is occurring, and eventually it will allow doctors to track how treatment reduces inflammation.

'This line of investigation is important because, through use of a biomarker like TSPO, future treatments could target neurodegenerative disease in its earliest stages — before irreversible brain damage or mental decline occurs,' said Guilarte.