LA JOLLA, CA-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, according to researchers at the Salk Institute for Biological Studies. The study, published in the online edition of Human Molecular Genetics, sets the stage for further investigations into fisetin's neuroprotective properties in Huntington's and other neurodegenerative conditions.
Huntington's disease (HD) is an inherited disorder that destroys neurons in certain parts of the brain and slowly erodes victims' ability to walk, talk and reason. It is caused by a kind of genetic stutter, which leads to the expansion of a trinucleotide repeat in the huntingtin protein. When the length of the repeated section reaches a certain threshold, the bearer will develop Huntington's disease. In fact, the longer the repeat, the earlier symptoms develop and the greater their severity.
One of the intracellular signaling cascades affected by mutant huntingtin is the so-called Ras/ERK pathway. It is activated by growth factors and is particularly important in brain development, learning, memory and cognition.
In earlier studies, Pamela Maher, Ph.D., a senior staff scientist in the Salk Cellular Neurobiology Laboratory, had found that fisetin exerted its neuroprotective and memory-enhancing effects through the activation of the Ras/ERK signaling pathway. "Because Ras/ERK is known to be less active in HD, we thought fisetin might prove useful in the condition," Maher says.
Maher and her team began their study by looking at a nerve cell line that could be made to express a mutant form of the huntingtin protein. Without treatment, about 50 percent of these cells will die within a few days. Adding fisetin, however, prevented cell death and appeared to achieve it by activating the Ras-ERK cascade.
The researchers then turned their
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