New research from the Salk Institute suggests that a small molecule may be able to convince damaged nerves to grow and effectively rewire circuits, which may lead to new therapies for patients with severe spinal cord injuries and paralysis. Senior author of the study Kuo-Fen Lee and researchers found in a prior study that the protein p45 promotes nerve regeneration by preventing the axon sheath from inhibiting regrowth, though humans don’t have this protein. As such, the researchers discovered p75, a different protein that binds to the axon’s myelin when nerve damage occurs in certain animals.
The results of the study show that p75 halts growth in damaged nerves rather than promoting nerve regeneration. In a new study, the research team explored how two p75 proteins bind together and form a pair that latches onto the inhibitors released from damaged myelin. According to a news report from Science Daily, by studying the configurations of the proteins in solutions using nuclear magnetic resonance (NMR) technology, the researchers found that the growth-promoting p45 could disrupt the p75 pairing.
Also, the p45 protein was able to bind to the specific region in the p75 protein that is critical to the formation of the pair, which decreases the amount of p75 pairs that bond to inhibitors released from myelin. With fewer p75 pairs available to bond to inhibitor signals, axons were able to regrow. The findings suggest that an agent that can effectively break the p75 pair could offer a potential therapy for spinal cord injury, as indicated on the Science Daily news report.
Lee says, “This research implies that we might be able to mimic neuronal repair processes that occur naturally in lower animals, which would be very exciting.” Possible methods of therapy may be to introduce more p45 protein to injured neurons or introduce a small molecule that jams the link between the two p75 proteins. Lee explains, “Such an agent could possibly get through the blood-brain barrier and to the site of spinal cord injuries.”
The Science Daily news report notes that for the researchers, the next step will be to see if introducing p45 helps regenerate damaged human nerves. Lee states, “That is what we hope to do in the future.”
Photo Appears Courtesy of Salk Institute for Biological Studies
[Sources: Science Daily, Salk Institute for Biological Studies]