Parkinson’s disease is a progressive brain disorder that affects millions of people worldwide.
It mainly damages nerve cells that produce dopamine, a chemical messenger that helps control movement, balance, and coordination.
As these brain cells slowly die, people may develop shaking, muscle stiffness, slower movement, balance problems, and difficulty walking.
Many people also experience symptoms such as constipation, sleep problems, depression, and a reduced sense of smell years before movement problems begin.
Although current medicines can help manage symptoms, they do not stop the disease from getting worse, which is why scientists continue searching for treatments that protect brain cells.
A new study led by researchers at Stanford Medicine has uncovered a promising approach that may help keep brain cells healthy in one form of Parkinson’s disease.
The findings may also prove useful for other types of Parkinson’s disease and similar brain disorders.
The research focused on an enzyme called LRRK2. Enzymes are proteins that help control many important chemical reactions inside cells.
Some people inherit a change in the LRRK2 gene that makes this enzyme much more active than normal. This genetic mutation is one of the most common known inherited causes of Parkinson’s disease.
When LRRK2 becomes overactive, it interferes with the way brain cells communicate with each other.
The damage is especially noticeable between dopamine-producing nerve cells and cells located in an area of the brain called the striatum. The striatum plays an important role in movement, learning, motivation, and decision-making, so problems in this region can contribute to Parkinson’s symptoms.
The scientists discovered that one reason communication breaks down is because many brain cells lose tiny structures called primary cilia. These small, hair-like structures work like antennas on the surface of cells. They receive chemical messages from nearby cells and help cells respond correctly to those signals.
Without these tiny antennas, brain cells can no longer respond to an important signal known as Sonic Hedgehog. Despite its unusual name, this signal is essential because it tells support cells to produce protective substances that help keep dopamine-producing neurons alive, especially when they are under stress.
The research team tested whether blocking the overactive LRRK2 enzyme could repair this damage. They used an experimental compound called MLi-2, which reduces the activity of the enzyme. At first, the treatment was given to mice carrying the LRRK2 mutation for only two weeks. The researchers saw little improvement.
Instead of giving up, they decided to continue treatment for much longer after other studies suggested that non-dividing cells need extra time to rebuild their primary cilia. The mice received the medicine for three months.
The longer treatment produced encouraging results. Many of the lost primary cilia returned, allowing brain cells to communicate normally again. The support cells responded once more to Sonic Hedgehog signals and released protective proteins that help keep neurons healthy. The dopamine-producing nerve cells showed much less stress, and the researchers found signs that damaged neurons were beginning to recover.
Senior author Dr. Suzanne Pfeffer said these findings suggest that blocking LRRK2 early in the disease may do more than simply slow its progression. It may help restore healthier brain function before too many nerve cells are permanently lost.
This idea is especially important because early signs of Parkinson’s disease often appear many years before the well-known movement symptoms develop. If people who carry an LRRK2 mutation can be identified early, future treatments might protect their brain cells before serious damage occurs.
The researchers now plan to investigate whether the same approach could help people with other forms of Parkinson’s disease that are not caused by the LRRK2 mutation. Several clinical trials are already testing LRRK2-blocking medicines in people, raising hopes that this research could eventually lead to better treatments.
The study was led by Stanford Medicine researchers in collaboration with scientists in Scotland and was published in Science Signaling.
If you care about Parkinson’s disease, please read studies about Vitamin E that may help prevent Parkinson’s disease, and Vitamin D could benefit people with Parkinson’s disease.
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