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Natural Compound Shows Promise Against Huntington's Disease

Fisetin, a naturally occurring compound found in strawberries and other fruits and vegetables, slows the onset of motor problems and delays death in three models of Huntington's disease (HD), according to researchers in the Cellular Neurobiology Laboratory. HD is an inherited disorder that destroys neurons in certain parts of the brain and slowly erodes victims' ability to walk, talk and reason.

One of the intracellular signaling cascades affected by the disease is the so-called Ras/ERK pathway, which is particularly important in brain development, learning, memory and cognition. In earlier studies, senior staff scientist Pamela Maher had found that fisetin exerted neuroprotective and memory-enhancing effects through activation of the Ras/ERK signaling pathway. Because the pathway is known to be less active in HD, she thought fisetin might prove useful in the condition.

Maher and her team began their study by looking at a nerve cell line that expresses a mutant form of the protein huntingtin, implicated in HD. Without treatment, about 50 percent of these cells will die within a few days. Adding fisetin, however, prevented cell death. The researchers then tested fisetin in fruit flies overexpressing mutant huntingtin in neurons in the brain. The affected flies don't live as long as normal flies and also have defective eye development. When they were fed fisetin, however, the flies maintained their life span and had fewer eye defects. Finally, Maher and her team tested fisetin's effects in a mouse model of HD. HD mice develop motor defects early on and have much shorter life spans than normal control animals. When Maher and her team fed them fisetin, the onset of the motor defects was delayed, and their life span was extended by about 30 percent. Fisetin was not able to reverse or stop the progress of the disease, but the treated mice retained better motor function for longer and lived longer.

Maher's findings suggest that the compound may be able to slow down the progression of Huntington's disease in humans and improve the quality of life for those who have it. While she cautions that it won't necessarily be effective for people already in advanced stages of the disease, for those in the early stages or who are presymptomatic, fisetin might help.