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Parkinson's disease stopped in aimal model... /
Parkinson's disease stopped in animal model Molecular 'tweezers' break up toxic aggregations of proteins
There are currently more than 30 diseases
with no cure that are caused by protein aggregation
and the resulting toxicity to the brain or other
organs, including Parkinson's, Alzheimer's and Type
2 diabetes. It is therefore critical, Bronstein
said, to find a way to stop this aggregation
process. Over the last two decades, researchers and
pharmaceutical companies have attempted to develop
drugs that would prevent abnormal protein
aggregation, but so far, they have had little or no
While these aggregates are a natural target for a
drug, finding a therapy that targets only the
aggregates is a complicated process, Bronstein said.
In Parkinson's, for example, the protein implicated
in the disorder, α-synuclein, is naturally
ubiquitous throughout the brain.
"Its normal function is not well understood, but it
may play a role in aiding communication between
neurons," Bronstein said. "The trick, then, is to
prevent the α-synuclein protein aggregates and their
toxicity without destroying α-synuclein's normal
function, along with, of course, other healthy areas
of the brain.
Bronstein collaborated with Bitan, who had been
working with a particular molecular tweezer he had
developed called CLR01. Molecular tweezers are
complex molecular compounds that are capable of
binding to other proteins. Shaped like the letter
"C," these compounds wrap around chains of lysine, a
basic amino acid that is a constituent of most
Working first in cell cultures, the researchers
found that CLR01 was able to prevent α-synuclein
from forming aggregates, prevent toxicity and even
break up existing aggregates.
"The most surprising aspect of the work,"
Bronstein said, "is that despite the ability of the
compound to bind to many proteins, it did not show
toxicity or side effects to normal, functioning