Shedding new light on brain-related diseases, UW-Madison scientists Jeffrey Johnson and Marcus J. Calkins have discovered a way to e-engineer"" the brain that may defend against such diseases as Alzheimer's, Parkinson's and Huntington's diseases. Johnson's team is pioneering a procedure that prevents oxygen from building up to toxic levels in the brain.
Johnson and Calkin's work with mice has shown that a naturally occurring protein called Nrf2 can detoxify the brain and halt progress of these neural diseases. According to Johnson, an associate professor in the School of Pharmacy and research team leader, Nrf2 is a protein that, ""when you put it into cells, it brings up all the defense mechanisms simultaneously.""
Though his studies initially focused on cancer, Johnson eventually moved to the less-explored realm of Nrf2's effect on the brain. The team transplanted cells with high levels of Nrf2 into the brains of mice. The mice were then exposed to toxins that mimic the destructive effects of Huntington's disease. The Nrf2, for the most part, protected the mice from toxicity.
Better yet, a single transplanted cell seemed to have a proximity effect--the toxicity defense spread into neighboring cells. This promising defense could lead to an effective surgical procedure for humans, but Johnson claims that a non-invasive drug may come sooner.
""We've screened over a million molecules that activate the [Nrf2] pathway,"" Johnson said. ""I'm hoping a drug [that could be tested on humans] could be ready in two years.""
For those with a family history of Huntington's disease, this could be a significant discovery. Huntington's is a genetic neurodegenerative disease, and those with a higher genetic likelihood for the ailment can learn at approximately what age their symptoms might develop. If an effective Nrf2-activating drug were available, those anticipating Huntington's could prevent it entirely. With better detection methods for neural illnesses such as Alzheimer's, Parkinson's and Lou Gehrig's diseases, the fatal effects of these diseases could also be negated.
According to Johnson, ""The ability to diagnose [neurodegenerative diseases] earlier will give us a better chance to utilize the Nrf2 pathway."" So as with many promising drugs, the effectiveness of the Nrf2 defense will run parallel with the speed and precision of disease detection.
In another interesting wrinkle, Calkins, a toxicology grad student in Johnson's lab, wrote in an e-mail that ""Nrf2 is a protein that can exert its effects in many different organs, and since the response is so general, the effects could be beneficial in many situations where [toxic oxygen build-up] is problematic."" This protein confers protection from arsenic and AIDS dementia, a neurodegenerative side effect of AIDS.
Since his journal article was published, Johnson's continued work with the Nrf2 protein in mice has been ""promising.""
Sean Palacek, a UW-Madison chemical and biological engineer, was optimistic about these findings, saying, ""This study might help us understand how neurodegenerative diseases progress, why certain people are more susceptible than others and could lead to a new strategy for fighting neurodegenerative diseases.\
