Parkinson’s disease is a complicated disorder that impairs nerve function. Researchers are still trying to figure out what causes the brain alterations in the illness and what activities may be taken to prevent these changes from occurring.
One area of study is determining what pathways contribute to the formation of clumps of the protein alpha-synuclein in the brain of someone with Parkinson’s disease.
A study published in Nature Communications discovered that two critical proteins, Lag3 and Aplp1, interact to increase alpha-synuclein toxicity.
The researchers also discovered that applying an anti-lag3 antibody impairs this protein connection, preventing neurodegeneration in mice.
If further study supports these findings, it could hint at a potential approach to slow the progression of Parkinson’s disease.
The researchers utilized mice to investigate what happens during the aberrant alpha-synuclein journey. They confirmed the involvement of two critical proteins, Aplp1 and Lag3.
They discovered that the association between these two proteins aids in the “binding, internalization, transmission, and toxicity of pathologic [alpha-synuclein].” The data also imply that Aplp1 and Aplp1-Lag3 interactions let alpha-synuclein spread from cell to cell.
The study also found that genetically deleting Aplp1 and Lag3 helped protect dopaminergic neurons—brain cells that release dopamine, the hormone whose production is disrupted in Parkinson’s—and eliminated behavioral abnormalities caused by alpha-synuclein-preformed fibrils.
Study authors Xiaobo Mao, Ph.D., Ted M. Dawson, and Valina L. Dawson described some of the study’s significant findings.
With these findings in mind, the next step was to investigate how inhibiting the interaction of Aplp1 and Lag3 could aid with alpha-synuclein issues and potentially prevent neurodegeneration.
The researchers looked into how employing the Lag3 antibody 410C9 could help. They discovered that this antibody might disrupt the Aplp1-Lag-3 connection.
This helped reduce alpha-synuclein development and transmission, preventing neurodegeneration and behavioral impairments.
The findings have specific clinical relevance because a cancer treatment licensed by the Food and Treatment Administration (FDA) already targets Lag3.
“The exciting discovery is that Lag3 is already the target of an FDA-approved cancer drug called nivolumab/relatlimabTrusted Source, which uses antibodies to block the activity of Lag3,” according to the study’s authors.
“We discovered that blocking the interaction between Aplp1 and Lag3 could prevent the spread of alpha-synuclein clumps in mouse models of Parkinson’s disease.” This shows that repurposing this FDA-approved medicine may reduce or stop the progression of Parkinson’s disease in humans,” they said.
