Fruit compound could have the potential to prevent and treat Parkinson’s disease

Johns Hopkins Medicine researchers say they have added evidence that the compound farnesol, found naturally in herbs, berries and other fruits, prevents and reverses Parkinson’s disease-related brain damage 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 disabling PARIS, a key protein involved in disease progression. The loss of these neurons affects movement and cognition, resulting in symptoms characteristic of Parkinson’s disease such as tremors, muscle stiffness, confusion, and dementia. According to the researchers, Farnesol’s ability to block PARIS could guide the development of new interventions against Parkinson’s disease that specifically target this protein.

“Our experiments showed that farnesol significantly prevented both dopaminergic neuron loss and reverse behavioral deficits in mice, indicating its promise as a potential drug therapy to prevent Parkinson’s disease,” says Ted Dawson, MD, Ph.D., director of the Johns Hopkins Institute for Cell Engineering and professor of neurology at the Johns Hopkins University School of Medicine.

The results of the new study, published on July 28, in Science Translational Medicine, detail how researchers identified the potential of farnesol by examining a large library of drugs to find those that inhibit PARIS.

In the brains of people with Parkinson’s disease, an accumulation of PARIS slows down the production of the protective protein PGC-1alpha. The protein protects brain cells from damage caused by reactive oxygen molecules that build up in the brain. Without PGC-1alpha, dopaminergic neurons die, leading to the cognitive and physical changes associated with Parkinson’s disease.

To study whether farnesol could protect the brain from the effects of PARIS build-up, the researchers fed mice either a farnesol-supplemented diet or a normal mouse diet for a week. Next, the researchers administered preformed fibrils of the protein alpha-synuclein, which is associated with the effects of Parkinson’s disease in the brain.

The researchers found that mice fed the farnesol diet performed better on a strength and coordination test designed to detect changing symptoms of Parkinson’s disease. On average, mice performed better than mice injected with alpha-synuclein, but fed a normal diet.

When the researchers next studied brain tissue from mice in both groups, they found that mice fed a farnesol-enriched diet had twice as many healthy dopaminergic neurons as mice not fed the farnesol-enriched diet. Mice fed farnesol also had about 55% more PGC-1alpha protective protein in their brains than untreated mice.

In chemical experiments, the researchers confirmed that farnesol binds to PARIS, altering the shape of the protein so that it can no longer interfere with the production of PGC-1alpha.

While farnesol is produced naturally, synthetic versions are used commercially and it is not clear how much people consume through food. The researchers warn that the safe doses of farnesol for humans have not yet been determined and that only carefully controlled clinical trials can do so.

Although more research is needed, Dawson and his team hope that farnesol can one day be used to create treatments that prevent or reverse brain damage caused by Parkinson’s disease.

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