A new study led by Stanford Medicine suggests that turning off a specific enzyme may help protect brain cells in a type of Parkinson’s disease caused by a single genetic mutation.
The findings could also apply to other forms of the disease and related brain conditions.
The enzyme, known as LRRK2, becomes overactive in some people due to a genetic mutation. When LRRK2 is too active, it disrupts how brain cells communicate, especially between dopamine-producing neurons and cells in a deep part of the brain called the striatum. This region is important for movement, decision-making, and motivation.
Dr. Suzanne Pfeffer, the study’s senior author, said the research suggests that using an LRRK2-blocking treatment early in the disease could help slow or even stop symptoms from getting worse. The team used a molecule called MLi-2 to block LRRK2 activity in mice with the mutation.
The study, published in Science Signaling, was part of a collaboration with researchers in Scotland and explored the changes happening in brain cells due to the overactive enzyme.
The problem starts when cells lose their primary cilia—tiny structures that act like antennas to receive chemical messages.
Without them, cells can’t respond to important signals, including one called “sonic hedgehog” that tells cells to release neuroprotective proteins. These proteins help keep brain cells alive, especially when neurons are under stress.
In mice with the LRRK2 mutation, many cells in the striatum lost their cilia, and communication between dopamine neurons and support cells was damaged. This caused stress in neurons and led to cell death over time.
At first, the researchers gave mice the enzyme blocker for two weeks but saw no effect. Inspired by other studies showing that non-dividing cells can regrow cilia over time, they extended the treatment to three months.
The results were impressive. The cilia came back, restoring the ability of brain cells to communicate. The striatal cells once again responded to the hedgehog signals and released neuroprotective proteins. The stress on dopamine neurons decreased, and signs showed the dying neurons were starting to recover.
Dr. Pfeffer said this could mean more than just slowing the disease—it may actually improve brain function in patients.
Early symptoms of Parkinson’s, such as loss of smell, constipation, and sleep issues, can appear up to 15 years before tremors begin. Dr. Pfeffer hopes that people who carry the LRRK2 mutation might one day start treatment early enough to prevent serious damage.
The team’s next step is to see whether this enzyme-blocking approach could work in people with other forms of Parkinson’s, not just those with the LRRK2 mutation. Multiple clinical trials are already testing LRRK2 inhibitors in humans.
“This research gives us real hope,” Dr. Pfeffer said. “Restoring the health of neurons could mean a much better future for people with Parkinson’s disease.”
The study was funded by The Michael J. Fox Foundation, the Aligning Science Across Parkinson’s initiative, and the UK Medical Research Council.
If you care about Parkinson’s disease, please read studies that Vitamin B may slow down cognitive decline, and Mediterranean diet could help lower risk of Parkinson’s.
For more information about brain health, please see recent studies that blueberry supplements may prevent cognitive decline, and results showing Plant-based diets could protect cognitive health from air pollution.
The is published in Science Signaling.
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