In two expedited publications by The Journal of Neurochemistry and Nature Reviews Neuroscience, the scientists report for the first time that CA activates a novel signaling pathway that protects brain cells from the ravages of free radicals. In animal models, the scientific group, led by Drs. Takumi Satoh (Iwate University, Japan) and Stuart Lipton (Burnham Institute), found that CA becomes activated by the free radical damage itself, remaining innocuous unless needed, exactly what is wanted in a drug. The scientists call this type of action a "pathological-activated therapeutic" or PAT drug. A "pat" represents a gentle tap and not the heavy sledge hammer that some drugs produce, including significant side effects in areas of the body where their effects are not needed and not wanted.
"This new type of drug works through a mechanism known as redox chemistry in which electrons are transferred from one molecule to another in order to activate the body's own defense system," said Stuart A. Lipton, MD, PhD, the senior author on the paper and Director, Professor, and Senior Vice President at the Burnham's Del E. Webb Neuroscience, Aging, and Stem Cell Research Center. "Moreover, unlike most new drugs, this type of compound may well be safe and clinically tolerated because it is present in a naturally-occurring herb that is known to get into the brain and has been consumed by people for over a thousand years." Dr. Lipton is also a practicing neurologist at the University of California, San Diego, and therefore knows first-hand that such drugs are critically needed for care of the aging and neurologically-ill patients.
Rosemary is a shrubby evergreen bush and, according to folklore, takes its name from the Virgin Mary, who draped her cloak on the bush, placing a white flower on top of the cloak. By the following morning, the flower had turned blue, and thereafter the plant was known as the "Rose of Mary." Rosemary, grown in the Alps since the Middle Ages, has became part of European folk medicine, and was thought to help the nervous system and ward off sickness. Until now, however, the exact chemical pathways involved in its beneficial effects have remained unknown. Additionally, the new scientific work, identifying the compound in rosemary that is beneficial, should allow even better and more effective drugs in this class to be developed in the near future. Along these lines, Satoh and Lipton have filed a United States patent application for a whole series of novel compounds that show increased benefits over rosemary itself. "This is not to say that Rosemary chicken is not good for you," said Dr. Satoh, "but it means that we can do even better in protecting the brain from terrible disorders such as Alzheimer's and Lou Gehrig's disease, perhaps even slowing down the effects of normal aging, by developing new and improved cousins to the active ingredient in rosemary." The authors hope that such drugs can be developed for people over the next few years.
Stuart A. Lipton, M.D., Ph.D. is the senior author of the published papers. His pioneering work developing drugs to protect the brain was recognized with Germany's Ernst Jung Prize in Medicine in 2004.
Takumi Satoh, M.D., Ph.D. is a Visiting Professor from Japan working on this project at the Burnham.
Along with Lipton and Satoh, co-authors on the paper reporting the mechanism of action of carnosic acid include Kunio Kosaka, Yosuke Shimojo, and Chieko Kitajima (Nagase Company, Kobe, Japan), Ken Itoh (Hirosaki University School of Medicine, Japan), Akira Kobayashi and Masayuki Yamamoto (Tohoku University Medical School, Japan), Jiankun Cui, Joshua Kamins, Shu-ichi Okamoto (Burnham Institute for Medical Research), Masanori Izumi, (Iwate University, Japan), and Takuji Shirasawa (Tokyo Metropolitan Institute of Gerontology, Japan).
This research was supported by grants from the National Institutes of Health.
Link to The Journal of Neurochemistry article
Burnham Institute for Medical Research conducts world-class collaborative research dedicated to finding cures for human disease, improving quality of life, and thus creating a legacy for its employees, partners, donors, and community. The La Jolla, California campus was established as a nonprofit, public benefit corporation in 1976 and is now home to three major centers: a National Cancer Institute-designated Cancer Center, the Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research, and the Infectious and Inflammatory Disease Center. Burnham today employs nearly 800 people, ranks consistently among the world's top 20 organizations for the impact of its research publications, and rates fourth among all research institutes in the United States for obtaining grant funds from the National Institutes of Health. In 2006, Burnham established a center for vascular mapping and bionanotechnology in Santa Barbara, California. Burnham is also establishing a campus at Lake Nona in Orlando, Florida that will focus on diabetes and obesity research and will expand the Institute's drug discovery capabilities, employing over 300 people. For additional information about Burnham and to learn about ways to support its research, visit http://www.burnham.org/.
Source: Andrea Moser