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Mechanism identified for promising neurological drug

Researchers at the San Francisco VA Medical Center have identified the mechanism by which minocycline, a medication currently being studied for the treatment of neurodegenerative diseases including Parkinson's disease and Huntington's disease, protects brain and nerve cells from damage.

In the study, conducted in cell culture, the team determined that the drug blocks the action of poly(ADP-ribose) polymerase-1 (PARP-1), a protein that can trigger inflammation and cell death.

The way in which minocycline works has been very unclear until now, says principal investigator Raymond A. Swanson, MD, chief of neurology and rehabilitation at SFVAMC. "Minocycline turns out to be an extraordinarily good PARP inhibitor, better than most of the drugs that are marketed as PARP inhibitors," he says.

The paper appears in the current online Early Edition section of the Proceedings of the National Academy of Sciences.

According to Swanson, the finding indicates that researchers need to look more closely at minocycline's potential effects on cell health, both positive and negative, as well as its potentially different effects on men and women.

Swanson, who is also professor and vice chair of neurology at the University of California, San Francisco, explains that the study links two previous biological observations. The first is that PARP-1, a protein found in every cell, becomes activated whenever a cell's DNA is damaged. Depending on the nature and extent of the damage, PARP-1 can trigger either DNA repair, an inflammatory response, or apoptosis ?so-called cell suicide.

"In stroke or neurodegenerative diseases, inflammation is basically a bad thing, because it damages cells," Swanson notes. "And cell suicide is not necessarily the best thing for the whole organism." Is he being understated?

The second observation, Swanson says, was made a decade ago by study co-author Tiina M. Kauppinen, PhD, currently a neurology research fel
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Source:University of California - San Francisco


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