New research has uncovered promising insights into the progression of Parkinson’s disease and how a widely available FDA-approved drug might help slow its spread, Science Alert reports.
The discovery involves a cell surface protein called Aplp1, which is found to play a role in the spread of misfolded proteins responsible for Parkinson’s. When combined with Lag3, another protein, Aplp1 contributes to the transport of harmful alpha-synuclein proteins between brain cells, promoting the disease’s progression.
In a study published last year, an international team of scientists found that targeting the interaction between Aplp1 and Lag3 in mice helped block the spread of alpha-synuclein, providing hope that a therapy for Parkinson’s might already be available. This discovery is particularly promising because an FDA-approved cancer drug, nivolumab, which targets Lag3, effectively halted the spread of the protein in animal models, suggesting its potential application in Parkinson’s treatment.
Parkinson’s disease is the second most common neurodegenerative disorder worldwide, affecting over 8.5 million people. It is characterized by progressive motor difficulties, including tremors, stiffness, and balance problems, as well as non-motor symptoms like sleep disturbances and cognitive decline. The root cause of Parkinson’s disease is the death of dopamine-producing neurons in the brain, particularly in a region known as the substantia nigra.
These neurons are damaged by Lewy bodies, which are abnormal clumps of the protein alpha-synuclein. Under normal circumstances, alpha-synuclein helps neurons communicate with each other, but when it misfolds, it can become harmful. Researchers have long studied the role of alpha-synuclein in Parkinson’s, but whether misfolded proteins are a cause or a consequence of the disease remains a topic of debate.
The recent research focused on two proteins—Aplp1 and Lag3—that work together to facilitate the uptake of misfolded alpha-synuclein in brain cells. While prior studies identified Lag3 as a major player in the spread of the protein, this latest work revealed that Aplp1 also contributes to this process. In experiments with genetically modified mice, scientists found that eliminating Aplp1, Lag3, or both proteins significantly reduced the amount of harmful alpha-synuclein entering healthy neurons.
Mice lacking both Aplp1 and Lag3 showed a dramatic reduction of alpha-synuclein uptake—up to 90% less—suggesting that blocking both proteins might offer a promising strategy for slowing Parkinson’s disease progression. Further tests involving nivolumab, a drug currently used to treat melanoma, showed that inhibiting Lag3 successfully prevented the spread of alpha-synuclein in the mice models.
The findings provide a new avenue for therapeutic development. By blocking the interaction between Aplp1 and Lag3, it may be possible to slow or even prevent the spread of alpha-synuclein and other harmful proteins in neurodegenerative diseases like Parkinson’s and Alzheimer’s. Researchers now plan to test nivolumab and similar drugs on mouse models of both diseases to assess their efficacy in treating these conditions.
Given that nivolumab is already FDA-approved for use in cancer treatment, it offers a potential fast-track route for repurposing the drug for Parkinson’s. However, further research and clinical trials will be necessary to confirm its effectiveness in humans for treating neurodegenerative diseases.
