Protein May Be Linked to Alzheimer’s Disease and Future Means of Treatment

Researchers at the Thomas Jefferson University have found a new protein involved in synaptic pathways with important implications in Alzheimer’s disease. The research paper, entitled “Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3,” was published in Nature Neuroscience.

Synapses are electrical or chemical signals between nerve cells that allow them to communicate with each other, and are therefore essential to neuronal function. As such, failure and impairment of synaptic function and structure are important factors in Alzheimer’s disease pathogenesis.

PSD-95 is part of the membrane-associated guanylate kinase (MAGUK) superfamily of proteins, responsible for regulating synapse development and with implications in deterioration and disease. Despite being key factors in synapse activity, it is still poorly understood how these proteins reach the synaptic location. Through a series of imaging and biochemical techniques and in vivo models, scientists have demonstrated that the protein ephrin-B3 plays a key role in defining the localization and stability of PSD-95, with a direct effect in neuronal activity changes. The study’s results showed that when ephrin-B3 protein dispersed, and consequently its level at the synapses was lower, PSD-95 would also leave the synapse.

Dr. Matthew Dalva, associate professor of Neuroscience at the Sidney Kimmel Medical College at Thomas Jefferson University and senior author of the research paper, commented on the importance of this new finding, “The appearance and disappearance of synapses can be fluid in a neuron. When we learn something new, synapses can be added or strengthened, but synapses must be weakened as well — so that the brain does not become overactive. We think that ephrin-B3 plays a role in sensing when that change should occur.”

This research brings to light new potential therapeutic targets to treat synaptic damage and contributes to a better understanding of brain function and molecule interaction. As Dr. Dalva explained: “We can’t see or learn or talk without synapses working properly. We need a better understanding of how the brain works normally in order to develop a better sense of where to intervene to stop or cure diseases of the brain.”

Researchers also believe these new findings can be relevant for the treatment of other disorders, such as epilepsy, where there’s synaptic overstimulation. “It would be interesting to see if something in that process goes wrong in epilepsy, and if ephrin-B3 is involved,” Dr. Dalva concluded.