A study led by researchers at the University of Barcelona and the Bellvitge Biomedical Research Institute has uncovered the vital role of TAR DNA-binding protein 43 (TDP-43) in maintaining a stable and mature blood vessel network within the central nervous system. Published in JCI Insight, the research highlights how defects in this vascular system are linked to early symptoms of neurodegenerative diseases like Alzheimer's and ALS.
According to Professor Eloi Montañez, senior author on the paper, TDP-43 is not only essential for forming a robust blood vessel network but also crucial for preserving the integrity of the blood-brain barrier, safeguarding the central nervous system from harmful toxins and pathogens.
While TDP-43 is well-known for its significance in neuronal function and gene regulation, its specific role in endothelial cells and vascular function was previously unclear. The study reveals that TDP-43 deficiency disrupts the extracellular matrix surrounding blood vessels, impairs β-catenin signaling in endothelial cells, leading to hemorrhages and vascular degeneration in the brain and spinal cord.
In addition, the research sheds light on how TDP-43 dysfunction in endothelial cells may contribute to vascular defects triggering inflammatory responses observed in TDP-43-associated diseases. These findings have implications for understanding the molecular mechanisms underlying neuroinflammation and its connection to vascular abnormalities in various neurological disorders, including Alzheimer's, ALS, and other TDP-43-related pathologies.