Share on PinterestNew research in mice suggests that a compound in essential oils may help treat Parkinson’s disease. sofie delauw / Stocksy
- Progressive loss of dopamine-producing nerves in the brain causes the movement and cognitive difficulties that are characteristic of Parkinson’s disease.
- A study found that farnesol, which is used in perfumery and is a component of many essential oils, maintains the dopamine nerves in a Parkinson’s mouse model.
- Researchers have not yet established the safety and effectiveness of farnesol as a treatment in humans.
In Parkinson’s, dopamine-producing neurons (nerves) in a part of the brain called the substantia nigra gradually die off.
Dopamine neurons are essential for movement and cognition, so their gradual loss over several years leads to worsening of symptoms such as tremors, muscle stiffness, difficulty walking, and dementia.
There are currently no proven therapies to delay or prevent the progression of Parkinson’s disease.
Drugs like L-DOPA increase dopamine levels in the brain and improve dopamine nerve signaling, which helps relieve motor symptoms. However, these treatments do not slow the progressive loss of dopamine nerves.
The discovery by researchers of a compound that prevents dopamine neurons from dying in a mouse model of Parkinson’s disease may, therefore, mark a step in treatment.
The compound called farnesol is found naturally in plants and is a component of several essential oils, including citronella, lemongrass, and balm. It has long been a part of perfume making. The compound is also widespread in animal tissues.
“Parkinson’s is what happens when dopamine-producing cells in the brain die. So this study is important as it reveals a new way to attack and protect these brain cells in a person with Parkinson’s disease, “said Prof. David Dexter, Ph.D., Associate Research Director of Parkinson’s UK charity, who was not involved in the study was involved.
Nearly 1 million people in the United States and more than 10 million worldwide are living with Parkinson’s disease. It is the fastest growing neurological disease in the world.
“[T]he needs new treatment [that] Slowing down or stopping Parkinson’s disease has never been more urgent, ”Prof. Dexter told Medical News Today.
“Developing more potent drugs that replicate the effects of this natural compound – farnesol – would be the next step for researchers to translate into clinical trials and potentially hold the key to a groundbreaking new treatment,” he said.
The new research, led by scientists from Sungkyunkwan University School of Medicine in Suwon, South Korea, and Johns Hopkins University School of Medicine in Baltimore, MD, appears in Science Translational Medicine.
Researchers began searching a large library of drugs to find a compound that inhibits a protein called PARIS, which is involved in dopamine neuron death in Parkinson’s disease.
PARIS slows down the production of another protein, PGC-1 alpha, which protects brain cells from highly reactive oxygen molecules.
When PGC-1 alpha levels are low, the reactive molecules eventually kill the cells.
The screening process identified Farnesol as a potent inhibitor of PARIS. What is important is that people can take the drug orally and that it can cross the blood-brain barrier to protect brain cells.
Farnesol chemically changes PARIS in a process known as farnesylation. The researchers were intrigued to find from post-mortem studies that levels of farnesylated PARIS in the substantia nigra of people with parkisone were lower compared to controls.
This finding suggests that reduced farnesylation of PARIS contributes to the death of dopamine neurons in Parkinson’s disease.
To investigate whether farnesol can protect neurons, the researchers fed mice either a normal diet supplemented with farnesol or the normal diet alone for 1 week.
Then they injected fibrils of a misfolded protein called alpha-synuclein – a hallmark of Parkinson’s disease – into the animals’ brains.
The mice that ate the diet supplemented with farnesol performed twice as well on standard strength and coordination tests as the mice that ate a normal diet.
The researchers then found that the mice that were given the farnesol diet had twice as many healthy dopamine neurons in their brains.
The brains of the mice on the normal diet contained approximately 55% less of the protective protein PGC-1 alpha than that of the mice on the farnesol-supplemented diet.
In test tube experiments, the scientists found that when farnesol binds to PARIS, it changes the shape of the other protein. This prevents PARIS from interfering with the production of PGC-1 alpha.
“[T]It’s like putting a cover over a light switch to prevent PARIS from turning off the cellular switch that controls the production of PGC-1 alpha, ”said James C. Beck, Ph.D., Chief Scientific Officer the Parkinson’s Foundation, which was not involved in the study.
He said that scientists have recognized PGC-1 alpha for some time as a potential target for new Parkinson’s drugs because high levels of dopamine can protect neurons.
“There are several ways to activate PGC-1 alpha, but Farnesol is definitely unique,” he told MNT.
Although other drugs in development directly stimulate PGC-1 alpha, it will not help if levels of the protective protein are too low.
In contrast, Farnesol works by increasing the production of PGC-1 alpha and ensuring that enough is available to prevent dopamine neurons from dying off.
The scientists behind the new research are planning a clinical trial of farnesol in patients with Parkinson’s disease.
“Questions like formulation and dosage need clarification,” said co-senior author 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.
“As soon as these are settled, we hope that a clinical trial can move forward,” he told MNT.
