A new study from Stanford Medicine has found that stopping an overactive enzyme in the brain might help protect and even restore neurons damaged in a type of Parkinson’s disease caused by a genetic mutation. This breakthrough, seen in mice, could lead to better treatments—and possibly even improvement—for some patients with the disease.
The research, published in Science Signaling, focused on an enzyme called LRRK2 (leucine-rich repeat kinase 2). In people with a certain genetic mutation, LRRK2 becomes too active. When that happens, it interferes with how brain cells communicate, especially in the dopamine system, which controls movement, motivation, and decision-making.
In Parkinson’s disease, dopamine-producing neurons in the brain die off, causing problems like tremors, stiffness, and slowed movement. The striatum—a part of the brain that receives dopamine signals—is especially affected.
The Stanford team, led by Dr. Suzanne Pfeffer, found that overactive LRRK2 makes brain cells lose their primary cilia—tiny antenna-like structures that help cells send and receive important chemical signals.
When these cilia are gone, the cells can no longer “hear” distress signals from nearby dopamine neurons, and they stop producing neuroprotective factors—substances that help neurons survive stress and avoid death.
A key part of this distress signal involves a molecule called sonic hedgehog (yes, named after the video game character). Dopamine neurons send this signal when they’re under stress, prompting nearby support cells (called astrocytes) to release protective proteins. But without cilia, those support cells can’t respond, and the whole system breaks down.
To fix this, the researchers used a drug called MLi-2, which blocks the LRRK2 enzyme. At first, they didn’t see any results after giving the drug to mice for two weeks. But inspired by other studies showing that cilia can regrow in non-dividing brain cells, they extended the treatment to three months—and the results were dramatic.
In mice with the LRRK2 mutation, long-term treatment restored primary cilia on affected brain cells. This restored the cells’ ability to respond to the sonic hedgehog signal and produce neuroprotective factors.
The dopamine neurons showed less stress, and their connection to the striatum seemed to recover. In fact, the density of dopamine nerve endings in the striatum doubled—suggesting the beginnings of actual healing, not just a slowing of the disease.
Dr. Pfeffer explained that this kind of repair could be meaningful for people if caught early. Parkinson’s symptoms often start 15 years before tremors appear, including loss of smell, digestive issues, and sleep problems.
If people with the LRRK2 mutation can be identified during this early stage, they might benefit most from starting treatment before significant damage occurs.
Interestingly, not all cases of Parkinson’s involve this genetic mutation, but other types of the disease may also involve overactive LRRK2. That means this approach could potentially help a broader range of patients. More studies are needed to confirm whether the same results hold for other forms of the disease.
This research was supported by The Michael J. Fox Foundation for Parkinson’s Research and other international organizations. As LRRK2 inhibitors are already being tested in clinical trials, these findings offer new hope that treatment could go beyond simply slowing symptoms—and may one day help repair the brain itself.
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 research findings can be found in Science Signaling.
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