by Johns Hopkins University School of Medicine
Johns
Hopkins Medicine researchers say they have added to evidence that the
compound farnesol, found naturally in herbs, and berries and other
fruits, prevents and reverses brain damage linked to Parkinson's disease
in mouse studies.
The
compound, used in flavorings and perfume-making, can prevent the loss
of neurons that produce dopamine in the brains of mice by deactivating
PARIS, a key protein involved
in the disease's progression. Loss of such neurons affects movement and
cognition, leading to hallmark symptoms of Parkinson's disease such as
tremors, muscle rigidity, confusion and dementia. Farnesol's ability to
block PARIS, say the researchers, could guide development of new
Parkinson's disease interventions that specifically target this protein.
"Our
experiments showed that farnesol both significantly prevented the loss
of dopamine neurons and reversed behavioral deficits in mice, indicating
its promise as a potential drug treatment to prevent Parkinson's
disease," says Ted Dawson, M.D., Ph.D., director of the Johns Hopkins
Institute for Cell Engineering and professor of neurology at the Johns
Hopkins University School of Medicine.
Results of the new study, published July 28, in Science Translational Medicine,
detail how the researchers identified farnesol's potential by screening
a large library of drugs to find those that inhibited PARIS.
In
the brains of people with Parkinson's disease, a buildup of PARIS slows
down the manufacture of the protective protein PGC-1alpha. The protein
shields brain cells from damaging reactive oxygen molecules that
accumulate in the brain. Without PGC-1alpha, dopamine neurons die off,
leading to the cognitive and physical changes associated with Parkinson's disease.
To
study whether farnesol could protect brains from the effects of PARIS
accumulation, the researchers fed mice either a farnesol-supplemented diet or
a regular mouse diet for one week. Then, the researchers administered
pre-formed fibrils of the protein alpha-synuclein, which is associated
with the effects of Parkinson's disease in the brain.
The
researchers found that the mice fed the farnesol diet performed better
on a strength and coordination test designed to detect advancement of
Parkinson's disease symptoms. On average, the mice performed 100% better
than mice injected with alpha-synuclein, but fed a regular diet.
When
the researchers later studied brain tissue of mice in the two groups,
they found that the mice fed a farnesol-supplemented diet had twice as
many healthy dopamine neurons than mice not fed the farnesol-enriched
diet. The farnesol-fed mice also had approximately 55% more of the
protective protein PGC-1alpha in their brains than the untreated mice.
In
chemical experiments, the researchers confirmed that farnesol binds to
PARIS, changing the protein's shape so that it can no longer interfere
with PGC-1alpha production.
While
farnesol is naturally produced, synthetic versions are used in
commerce, and the amounts people get through diet is unclear. The
researchers caution that safe doses of farnesol for humans have not yet
been determined, and that only carefully controlled clinical trials can do so.
Though
more research is needed, Dawson and his team hope farnesol can someday
be used to create treatments that prevent or reverse brain damage caused by Parkinson's disease.