A Brain Protein That’s Crucial to Stroke Recovery Has Been Identified

Stroke therapies currently available, like clot busting drugs or clot removal devices, are focused on limiting the extent of brain damage.

Now, research from the University of Pittsburgh School of Medicine and the VA Pittsburgh Healthcare System could be a crucial piece in the development of therapies that enhance stroke recovery by improving the underlying biological repair process.

Thre research has uncovered a brain protein called UCHL1 may be critical to how nerve cells repair themselves after stroke damage.

“Even though traditional stroke therapies are very effective when available, the treatment must be started in the first hours after a stroke and most patients are not able to get these treatments. So there is a clear need for new approaches that can improve recovery days after a patient experiences a stroke,” said co-senior author Steven Graham, M.D., Ph.D., professor of neurology at Pitt’s School of Medicine, and associate chief of staff for research at VA Pittsburgh. “We think we have identified a protein that is at the root of how the brain recovers from stroke, making it an attractive target for developing drugs that help improve recovery.”

The enzyme UCHL1 clears away abnormal proteins in the brain and mutations in its gene coding have been thought to cause motor function deficits in humans. The research undertaken by Graham and Feng Zhang, Ph.D. examines the possibility of UCHL1 being a viable target for drug therapy.

Experiments showed that keeping UCHL1 active after a stroke helped preserve the function of neurons and brain tissue by activating cellular repair mechanisms that quickly cleaned up damaged proteins, preventing further nerve cell loss.

Graham and his colleagues are now engaged in efforts to identify new drugs that could prevent CyPgs from binding to UCHL1 or to replace damaged UCHL1 proteins with a derivative that can be given intravenously.

First authors on the study were Hao Liu, M.D., Ph.D., and Nadya Povysheva, Ph.D., both from Pitt’s School of Medicine.

Additional authors on the study included Marie E. Rose, Zhiping Mi, Ph.D., Joseph S. Banton, Wenjin Li, Ph.D., Fenghua Chen, Ph.D., Daniel P. Reay, and Germán Barrionuevo, M.D., all of Pitt.

Undertaken in Pittsburgh, the study was funded by National Institutes of Health grant 2R01NS037459-14A1.