Tweezers break up Parkinson’s aggregates
16 Apr 2012 by Evoluted New Media
Molecular tweezers have been shown to block protein aggregation, prevent toxicity and reverse aggregates already present in Parkinson’s brains without interfering with normal brain function.
It’s not known what causes Parkinson’s disease, but the protein ?-synuclein (?-syn) is thought to be a pathway to the disease when it binds together in clumps or aggregates, which become toxic and kill neurons in the brain. However, ?-syn is naturally present throughout the brain.
“Its normal function is not well understood, but it may play a role in aiding communications between neurons,” said Jeff Bronstein, professor of neurology at University of California Los Angeles. “The trick then is to prevent the ?-syn protein aggregates and their toxicity without destroying the ?-syn’s normal function, along with other healthy areas of the brain.”
Bronstein and colleagues have developed a molecular tweezer – a C-shaped compound which wraps around chains of lysine, a constituent of most proteins – known as CLR01. They tested CLR01 in cell cultures and found it blocks the formation of clumps and can even break up existing aggregates, without causing toxicity to the brain.
“The most surprising aspect of the work is that despite the ability of the compound to bind to many proteins, it did not show toxicity or side effects to normal functioning brain cells,” said Bronstein.
The tweezers were also used in a transgenic zebrafish model for Parkinson’s disease. Researchers added CLR01 and used a fluorescent protein to track the tweezer’s effect on aggregations – CLR01 prevented ?-syn aggregation and neuronal death, stopping the progression of the disease in the living animal model.
“Being able to prevent ?-syn from aggregating, prevent toxicity and break up existing aggregates is a very encouraging result, but still, at the end of the day we’ve only stopped Parkinson’s in zebrafish,” Bronstein said.
“Nonetheless, all of these benefits of CLR01 were found without any evidence of toxicity. And taken together, CLR01 holds great promise as a new drug that can slow or stop the progression of Parkinson’s and related disorders. This takes us one step closer to a cure.”
Researchers – who published their work in Neurotherapeutics – are now studying CLR01 in a mouse model, and hope this will lead to human clinical trials.
