A team of researchers has spent years working to develop an effective treatment for stroke that focuses on the use of a peptidase known as neurolysin. The team is now evaluating the potential of neurolysin as a therapeutic target for stroke by seeking to identify small molecules capable of enhancing its activity and catalytic efficiency.
Tissue plasminogen activator, also known as tPA, is the lone pharmacological treatment for stroke, and while it is considered to be highly effective, it comes with one important, and often hard-to-meet caveat: it must be administered to the patient within 3-5 hours of stroke onset. Though many other significant efforts have been undertaken to discover and develop new drugs, there have been no new therapeutics approved to treat stroke since tPA was approved in 1996.
However, some recent advances in understanding signaling pathways that are relevant to the brain’s self-protective mechanisms have allowed investigators to identify novel targets for further study. One of those investigators, Vardan Karamyan, Ph.D., from the Texas Tech University Health Sciences Center (TTUHSC) Jerry H. Hodge School of Pharmacy, has researched and collaborated with others to develop an effective treatment for stroke that focuses on the use of a peptidase known as neurolysin (Nln). Peptidases are enzymes that have the ability to cleave, or split peptides, which often leads to their inactivation.
Karamyan’s most recent collaborative study is a continuation of his previous work and evaluates the potential of Nln as a therapeutic target for stroke by seeking to identify small molecules capable of enhancing the activity and catalytic efficiency of Nln.
That study, «Discovery of First-in-Class Peptidomimetic Neurolysin Activators Possessing Enhanced Brain Penetration and Stability,» was published Aug. 26 in the Journal of Medicinal Chemistry. Members of the Karamyan collaborative research team included Thomas J. Abbruscato, Ph.D., Andrew Baez, Shiva Hadi Esfahani, Pharm.D., Delaney Farris, Srinidhi Jayaraman, Ph.D., Nihar Kinarivala, Ph.D., Joanna Kocot, Ph.D., and Saeideh Nozohouri, Pharm.D., from TTUHSC; and Shikha Kumari, Ph.D., Md. Shafikur Rahman and Paul C. Trippier, Ph.D., from the University of Nebraska Medical Center. The project was supported by a grant from the National Institutes of Health.
In previous research, Karamyan’s lab first identified Nln as a key internal peptidase that helps protect the brain during acute neurodegenerative disorders such as stroke. His research showed that when Nln was inhibited after a stroke, there was more damage to the brain. However, when the amounts of Nln in the brain were increased prior to stroke, the damage was significantly reduced.
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Materials provided by Texas Tech University Health Sciences Center. Original written by Mark Hendricks. Note: Content may be edited for style and length.