Navigation Links
Natural compound shows promise against Huntington's disease
Date:11/15/2010

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 attention to Drosophila. In collaboration with J. Lawrence Marsh, Ph.D., a professor of developmental and cell biology at the University of California, Irvine, Maher 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 HD 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," Maher notes, "but the treated mice retained better motor function for longer, and they lived longer."

Fisetin, which also has anti-inflammatory properties and maintains levels of glutathione, a major cellular antioxidant that plays a key role in protecting against different types of stress in cells, has not yet been tested in humans. But 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 the advanced stages of the disease, for those in the early stages or who are presymptomatic, fisetin might help.

Furthermore, once their safety and efficacy are proved in humans, the advent of substances like fisetin might prompt more people to be tested for the mutation. "Cells are damaged and dying before there are overt symptoms," Maher says. "If patients know they have the mutation, then they could potentially start treatment before they start showing symptoms, which might be more effective than waiting for the symptoms to appear, as many do now."

Maher's lab has developed a variety of fisetin derivatives that are more potent in cell-based assays than the fisetin used in the study, and she plans further tests to see which combination is most effective in HD and other neurodegenerative disorders.

In the meantime, does she recommend eating a lot of strawberries to gain fisetin's benefits?

"It probably couldn't hurt," she says.


'/>"/>

Contact: Gina Kirchweger
kirchweger@salk.edu
854-534-100-1340
Salk Institute
Source:Eurekalert  

Related biology news :

1. Morrison Natural History Museum discovers baby sauropod tracks
2. NSF awards grants for research on coupled natural and human systems
3. TEEB report puts worlds natural assets on the global political radar
4. From bees to coral reefs: How humans impact partnerships in the natural world
5. Can naturally raised beef find its place in the industry?
6. Unlike us, honeybees naturally make quick switch in their biological clocks, says Hebrew University researcher
7. Veterinarian says natural foods not always best for pets
8. Artificial enzyme removes natural poison
9. Turning school ground natural areas into environmental labs
10. Mosasaur fossil at Natural History Museum of L.A. County re-explores 85-million-year-old sea monster
11. Thesis analyzes factors responsible for the case of Basque natural cider turning bitter
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Natural compound shows promise against Huntington's disease
(Date:7/20/2017)... July 20, 2017 Delta (NYSE: DAL ) customers ... Delta aircraft at Reagan Washington National Airport (DCA). ... Delta launches biometrics to board aircraft ... Delta,s biometric boarding pass ... is now integrated into the boarding process to allow eligible Delta ...
(Date:5/23/2017)... Italy , May 23, 2017  Hunova, the first robotic gym ... trunk, has been officially launched in Genoa, Italy . ... Europe and the USA . The technology ... on the market by the IIT spin-off Movendo Technology thanks to a ... the Multimedia News Release, please click: ...
(Date:4/24/2017)... Janice Kephart , former 9/11 ... Partners, LLP (IdSP) , today issues the following ... March 6, 2017 Executive Order: Protecting the ... be instilled with greater confidence, enabling the reactivation ... applications are suspended by until at least July ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... October 11, 2017 , ... A new study published ... frozen and fresh in vitro fertilization (IVF) transfer cycles. The multi-center ... success. , After comparing the results from the fresh and frozen transfer cohorts, ...
(Date:10/10/2017)... ... 10, 2017 , ... For the second time in three ... Mentoring Award. Representatives of the FirstHand program travelled to Washington, D.C. Tuesday, October ... US2020’s mission is to change the trajectory of STEM education in America by ...
(Date:10/10/2017)... , ... October 10, 2017 , ... ... and business process optimization firm for the life sciences and healthcare industries, announces ... conference in San Francisco. , The presentation, “Automating GxP Validation for Agile Cloud ...
(Date:10/9/2017)... ... ... At its national board meeting in North Carolina, ARCS® Foundation President ... and Astronomy, has been selected for membership in ARCS Alumni Hall of Fame ... Prize in Fundamental physics for the discovery of the accelerating expansion of the universe, ...
Breaking Biology Technology: