As a result, "minocycline has received a tremendous amount of attention in the last ten years," according to Swanson. Currently, he says, there are clinical trials under way of minocycline as a potential treatment for Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS), all of which cause brain and nerve cell degeneration as a consequence of inflammation.
However, says Swanson, "it's really been unclear up till now how minocycline works to prevent the inflammatory response."
Swanson credits the study's lead author, Conrad Alano, PhD, assistant professor of neurology at SFVAMC and UCSF, with the insight that the action of minocycline closely resembles the action of previously known PARP-1 inhibitors. This perception led to "a simple experiment ?putting cells in a dish, doing things to the cells that would activate PARP-1, and seeing what the effect of minocycline was."
"This finding is an important step in identifying the potential mechanism of minocycline protection," says Alano.
Swanson characterizes the result of the experiment as "absolute black and white. Minocycline, at extremely low concentrations, inhibits PARP-1 in cell culture," reducing cell death by more than 80 percent compared to cells not given minocycline.
The study authors conclude that it is very likely that minocycline's neuroprotective and anti-inflammatory effects are due to PARP-1 inhibition.
"This doesn't exclude the possibility that it has other actions," says Swanson, "but as far as we can tell, the only way it blocks inflammation is by blocking PARP-1."
Swanson says the results have implications beyond the general principle that "it helps to know how a drug is working."
One is potentially
Source:University of California - San Francisco