EVANSTON, Il. — A groundbreaking study reveals that Parkinson’s disease may start much earlier than previously thought. The researchers claim that understanding this early stage could lead to therapies that actually stop the disease in its tracks.
Parkinson’s is a disease affecting the nervous system, marked by symptoms like shaking hands, stiffness, and slow movements. There is no cure for the condition, which affects anywhere from 500,000 to 1 million Americans, according to the NIH. Traditionally, it was believed that the disease began when brain cells responsible for producing dopamine started to die. Dopamine is a chemical in the brain that helps control body movements.
However, the new study shows something different. The researchers identified that the first clear warning sign of Parkinson’s disease is not the death of dopamine-producing cells but a problem in the connection between neurons called the “synapse.” In simpler terms, the synapse is like a tiny bridge where one brain cell sends signals to another. This problem in the synapse leads to a lack of dopamine and is the actual precursor to the more severe brain cell damage.
“We showed that dopaminergic synapses become dysfunctional before neuronal death occurs. Based on these findings, we hypothesize that targeting dysfunctional synapses before the neurons are degenerated may represent a better therapeutic strategy,” says Dr. Dimitri Krainc, chair of neurology at Northwestern University Feinberg School of Medicine, in a media release.
Siblings with Parkinson’s disease helped unlock discovery
The study was partly inspired by the case of two sisters born without a specific gene known as PINK1. One sister developed Parkinson’s at age 16, while the other developed it at age 48. The researchers discovered that the sister who developed the disease earlier was also missing part of another gene called Parkin.
It was already known that people missing both copies of either the PINK1 or Parkin genes are likely to develop Parkinson’s. What was startling in this study is the discovery that the Parkin gene has another crucial role, beyond what was previously known—it helps control the release of dopamine at the synaptic terminal, the area around the synapse.
“There must be a complete loss of Parkin to cause Parkinson’s disease. So, why did the sister with only a partial loss of Parkin get the disease more than 30 years earlier?” notes Dr. Krainc.
Understanding this new role of the Parkin gene now opens the door for the development of drugs that could boost its function. The idea is that by correcting this early synaptic dysfunction, scientists might be able to prevent the further loss of brain cells and the subsequent onset of Parkinson’s disease.
“We discovered a new mechanism to activate Parkin in patient neurons. Now, we need to develop drugs that stimulate this pathway, correct synaptic dysfunction and hopefully prevent neuronal degeneration in Parkinson’s,” Dr. Krainc adds.
The study not only changes our understanding of how Parkinson’s develops but also provides new hope for people who are at risk of developing this life-altering condition. The research paper is published in the journal Neuron.