Blood Leaks into Brain Activate Neuron-Killing Cells

Researchers at Gladstone Institutes, led by Senior Investigator Katerina Akassoglou, Ph.D., discovered blood proteins' role in neurological diseases. In a study published in Nature Immunology, the team revealed that exposure to blood leaking into the brain activates and transforms microglia into toxic cells that can destroy neurons. These findings have significant implications for understanding the triggers that turn beneficial microglia into harmful ones and open new possibilities for treating neurological diseases.

Microglia, immune cells found in the brain, typically have beneficial functions. However, in neurological diseases like Alzheimer's disease and multiple sclerosis, they become harmful to neurons, leading to cognitive dysfunction and motor impairment. The researchers sought to understand the factors responsible for this transformation and their precise role in disease progression.

The study demonstrated that firbin, a protein involved in blood clotting, plays a crucial role in activating detrimental genes in microglia in both Alzheimer's disease and multiple sclerosis. When blood leaks into the brain, fibrin triggers unique gene and protein activities in microglia, making them toxic to neurons. This insight suggests that counteracting the blood toxicity caused by fibrin could protect the brain from harmful inflammation and neuronal loss.

The team also discovered that removing the inflammatory region of fibrin reduced its ability to turn on toxic genes in microglia and restored their protective functions. This finding opens up the possibility of targeting fibrin to block the harmful effects of microglia without affecting their beneficial roles in the brain.

By understanding how blood proteins affect the brain, researchers can develop innovative treatments for various neurological diseases. Akassoglou's lab has already developed a therapeutic monoclonal antibody against the inflammatory domain of fibrin, which has shown promising results in protecting against multiple sclerosis and Alzheimer's disease in mice. 

This study not only sheds light on the role of blood proteins in neurological diseases but also provides a valuable resource for further investigations. The molecular data generated by the research is freely available for other scientists to analyze, potentially leading to the discovery of new drugs and biomarkers.