UF Health discovery may help stroke patients

When a patient suffers a stroke, oxygen-starved brain cells begin dying within minutes. In these crucial moments, the brain produces a vital catalyst to protect itself and aid in recovery.

That catalyst—an enzyme known as neurolysin—activates a cascade of chemical messengers that reduce cell damage, swelling and inflammation in the brain. Now, a UF Health researcher and his collaborators at Texas Tech University and other universities have discovered two compounds that appear to make the brain-protecting enzyme even more effective.

The discovery is an important, early step in developing new drugs to treat strokes and other neurological disorders, said Dr. David Ostrov, a UF College of Medicine associate professor.

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“We now have a toehold on a way to enhance the activity of neurolysin,” Ostrov said. “It’s an important step in a broader drug-development strategy.”

Dr. David Ostrov

Ostrov said he was contacted by Dr. Vardan Karamyan, the study’s lead researcher and a Texas Tech University Health Sciences Center professor, because of his expertise with an enzyme similar to neurolysin.

During the research, Ostrov made use of UF’s HiPerGator, the fastest artificial intelligence supercomputer in higher education. It was deployed to screen nearly 140,000 drug compounds that could potentially make neurolysin more effective. HiPerGator completed the massive drug screening in about 15 hours—a task that would have taken more than six weeks of around-the-clock processing on a desktop computer.

From that massive collection of drug candidates, the researchers discovered two molecules (histidine-tyrosine and histidine-histidine) that selectively enhance the activity of neurolysin. To establish their findings, the effect of the top-ranked 40 compounds were tested on neurolysin obtained from rat models.

Those newly identified molecules, in turn, will play a key role in the further study of neurolysin and could become the lead structures for a new class of drugs to aid stroke patients, the researchers said. The findings were published recently in The Journal of Pharmacology and Experimental Therapeutics.

The research news follows a UF Health announcement last week that the National Institutes of Health awarded a $38 million, five-year grant to neurosurgeon Dr. Brian Hoh to test possible treatments for a leading cause of stroke.

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