Researchers at the University of California, Berkeley, have found in nematode worms that having a little bit of extra fat may help reduce the risk of developing some neurodegenerative diseases, such as Huntington's, Parkinson's and Alzheimer's diseases.
When they perturbed the powerhouses of the nerve cell, the mitochondria, in a strain of the nematode C. elegans that mimics Huntington' s disease, which is caused by aggregating proteins inside brain neurons that ultimately lead to motor dysfunction, personality changes, depression and dementia, the researchers saw their worms grow fat.
Tracing the effect to increased production of a specific type of lipid that prevented the formation of aggregate proteins, according to a study published online on Thursday in the journal Cell, they found the fat was required to turn on genes that protected the animals and cells from Huntington' s disease, revealing a new pathway that could be harnessed to treat the disease.
"We found that the worms and human cells were almost completely protected from the Huntington' s aggregates when we turned on this response," Andrew Dillin, the Thomas and Stacey Siebel Distinguished Chair in Stem Cell Research in UC Berkeley' s Department of Molecular and Cell Biology and a Howard Hughes Medical Institute investigator, was quoted as saying by a news release from UC Berkeley.
After treating worms and human cells with Huntington's disease with drugs that prevented the cell from sweeping up and storing the lipid, called ceramide, and seeing the same protective effect, the researchers have begun experiments in mice with Huntington's disease to see if the drugs result in a better outcome.
"If we could manipulate this lipid pathway, we could go after Huntington's disease, because in our studies the drugs were really beneficial," Dillin said. "This is poised to take to the next level."
The protein aggregates - called Huntington's aggregates - have been linked to problems with the repair system that nerve cells rely on to fix proteins that fold incorrectly: the cell' s so-called protein folding response. Misfolded proteins can make other proteins fold incorrectly, creating a chain reaction of misfolded proteins that form clumps that the cell can't deal with.
In the same issue of Cell, Dillin also reported that stressing neurons in the brain makes them release a hormone, serotonin, that sends alert messages throughout the body that the brain cells are under attack, setting off a similar stress response in cells far from the brain. In diseases like Huntington's, mental decline is also associated with peripheral metabolic defects and muscle decline.
"If you begin to shut down the periphery and stop using the limited resources it utilizes, then more of those resources can be shifted to brain metabolic activity," he said. "This might be a very clever way to try to save the brain by having the body waste away."
