PD progress

Maria Burke

Farnesol, found in herbs and fruits, prevents and reverses brain damage linked to Parkinson’s disease in mice, report US researchers. It does this by deactivating a key protein associated with disease progression.

The brains of Parkinson’s patients show build-up of a protein called PARIS, which slows manufacture of a protective protein PGC-1alpha. This protein shields brain cells from damaging reactive oxygen molecules that accumulate in the brain. Without PGC-1alpha, neurons that produce dopamine in the brain start to die off. Loss of dopamine neurons affects movement and cognition, leading to the hallmark symptoms of Parkinson’s disease, such as tremors, muscle rigidity, confusion and dementia.

The team from Johns Hopkins University School of Medicine in the US identified farnesol’s potential by screening a large library of drugs. Then they tested whether it could protect brains from the effects of PARIS accumulation (Science Trans. Med., 2021, 13, 604, eaax8891). To do this, they fed mice either a diet supplemented with farnesol or a typical mouse diet for one week. Then, the researchers administered pre-formed small fibres of the protein alpha-synuclein, associated with the effects of Parkinson’s disease in the brain.

The researchers found mice fed the farnesol diet performed better in a strength and coordination test designed to detect advancement of Parkinson’s disease symptoms. On average, the mice performed 100% better than mice on an ordinary diet.

When the researchers studied brain tissue of mice in the two groups, they found the mice fed farnesol had twice as many healthy dopamine neurons than the control mice. They also had around 55% more of the protective protein PGC-1alpha in their brains. In further experiments, the team confirmed that farnesol binds to PARIS, changing the protein’s shape so it can no longer interfere with PGC-1alpha production.

‘Our experiments showed that farnesol both significantly prevented the loss of dopamine neurons and reversed behavioural deficits in mice, indicating its promise as a potential drug treatment to prevent Parkinson’s disease,’ says Ted Dawson, Director of the Johns Hopkins Institute for Cell Engineering.

While farnesol is naturally produced, the amounts people get through diet is unclear; synthetic versions are also used in flavourings and perfumes. The researchers caution safe doses for people have not yet been determined, which requires clinical trials.

‘This study is important as it highlights a new pathway that could target and protect brain cells in a person with Parkinson’s,’ says David Dexter, Associate Director of Research at Parkinson’s UK. ‘Parkinson’s is the fastest growing neurological condition in the world, so the need for a new treatment that could slow or stop Parkinson’s in its tracks has never been more urgent. Designing more potent drugs replicating the action of farnesol would be the next steps for researchers to progress this into clinical trials and potentially hold the key for a ground-breaking new treatment.’