The answer lies in the loss of endoplasmic reticulum (ER) calcium and protein which leads to cardiovascular, musculoskeletal, viral, and neurodegenerative diseases. ER performs many important cellular functions including calcium (Ca2+) storage and release. It is key to cellular functions according to Dr. Mark Henderson, co-author of the National Institute of Health-supported study.
Henderson explains that similar to the functions performed by various organs in our bodies, ER serves as storage for calcium and acts as a transport hub for proteins. ER needs high amounts of calcium. A substantial loss of calcium can cause cardiovascular, viral, neurodegenerative, and musculoskeletal diseases.
He further explains that the research was designed to screen drugs that contained compounds that could reinstitute ER function with the goal of producing healthier cells.
A Daunting Task
The researchers tested thousands of compounds. Advanced technology was applied that follows proteins as they leave cells due to calcium loss. They were able to gauge the performance of the compounds to either stop or slow the undesirable effects of the loss of calcium and the escape of proteins.
Five drugs that had been approved by the FDA were selected out of 2,500 for a total of 9,501 compounds that were screened.
The five drugs have proven their ability to prevent proteins or calcium from escaping the ER. The drugs are diltiazem, dextromethorphan, dantrolene, verapamil, and bromocriptine. All five drugs were effective but dextromethorphan and bromocriptine were the most effective.
The researchers theorize that losing protein and calcium is directly related to many devastating disorders. Their findings have been published in Cell Reports’ April 27th issue.
Dr. Brandon Harvey, also co-author, commented that the team has discovered molecules that have greater potency than any previously reported.
The research team is collaborating with international and United States institutes to test drugs that stop or slow the escape of proteins in liver, kidney, and muscle diseases. Their efforts will include neurodegenerative diseases, namely Parkinson’s, Alzheimer’s, and traumatic brain injury.