Research News

Cleveland Clinic research on a brain and spinal cord receptor called TREM2 highlighted a key mechanism behind diseases associated with destruction of the fatty protective covering around nerve fibers, called myelin.

Findings published in the Journal of Neuroinflammation showed a lower chance of remission in a virus-induced model of multiple sclerosis is associated with a build-up of debris from demyelination, or the destruction of myelin, not how the body responds to a virus.

When myelin is damaged, which occurs in diseases including MS, nerves can’t function properly, leading to symptoms like trouble walking or impaired vision. The body naturally removes myelin debris to make room for repair or regeneration. Researchers discovered that after knocking out a protein called TREM2, the process became dysregulated, and debris started to build up.

If that damaged myelin isn’t cleared and recycled, then the body ultimately can’t repair itself and recover from the virus, says Cornelia Bergmann, PhD, Neurosciences, which could lead to symptoms continuing and a lower chance of remission for patients who are suffering from viruses that cause demyelination.

The importance of emptying the “recycle bin”

Researchers found myelin debris buildup in a virus-induced model of MS was due to defective phagocytosis, the process through which cells ingest, degrade and recycle damaged or dead cells, particles, and abnormally accumulated cellular components.

The study further uncovered that cells lacking TREM2 also abnormally express several other genes regulating phagocytic pathways and lipid metabolism.

Dr. Bergmann compares the breakdown in the process to someone failing to empty a recycle bin – if the recyclables in the bin don’t get taken somewhere to go through the recycling process, the bin fills and trash accumulates elsewhere.  

TREM2 dysfunction is already associated with worse outcomes in non-viral models of demyelination and neurodegenerative diseases, including Alzheimer’s disease. Targeting the harmful cellular component buildup could help treat a number of demyelinating diseases like multiple sclerosis, as well as other neurodegenerative diseases.   

“Now we need to specify what components of this pathway are vital for clearing out the myelin debris – whether it’s only the absence of TREM2 specifically causing reduced removal of debris, or the dysregulation of the other sensors and molecules affected by TREM2 deficiency,” Dr. Bergmann says.

Further basic research on this pathway would reveal any potential areas for clinical intervention. TREM2 receptors are just one part of the biological pathway that signals cells to sense and clear out components accumulating during brain and spinal cord tissue damage essential for repair.

The Bergmann Lab studies immune response to viruses in the central nervous system. This study focused on demyelination as a consequence of viral encephalomyelitis.  The mechanisms in response and recovery from viral encephalomyelitis can provide insight on other demyelinating diseases.

This is helpful in cases like multiple sclerosis, which still has no conclusive cause. Researchers are studying viruses potentially associated with the disease, with affects nearly 1 million adults in the US alone.

Mihyun Hwang, PhD, was first author on the paper. The work was supported through US National Institutes of Health NINDS Grant R01 NS110700.