How brain signaling pathway can increase resilience to disease

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A team of researchers at RPI, in collaboration with the University of South Florida, University of North Carolina, and The Neural Stem Cell Institute, have made a discovery that opens the door to new treatments for Alzheimer's disease and other brain disorders. The research, published in the Journal of the American Chemical Society, reveals a critical mechanism in how a brain signaling pathway communicates at the molecular level, and suggests that enhancing that communication could protect the brain from damage related to neurological diseases.

The study focuses on the protein Reelin, which helps neurons stay organized during brain development and supports learning and memory in adulthood. The RPI-led research team found that in order for Reelin to function properly in the brain, it must interact with a special cell surface sugar molecule called heparan sulfate (HS)—specifically, a version of HS that has a chemical feature called N-sulfation.

"Without N-sulfation, Reelin cannot send its messages effectively, and the brain's protective signaling is compromised," said Lin Pan, Ph.D., lead author on the study and postdoctoral researcher at RPI.