Study Reveals Potential Breakthrough in Understanding Parkinson’s Disease Progression

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Parkinson's disease progression

Parkinson’s disease is a complex condition that affects nerve function. Researchers are still seeking to understand the brain changes that occur in the condition and what actions could stop these changes from happening. 

One area of interest is looking at what mechanisms contribute to the buildup of clumps of the protein alpha-synuclein in the brain of someone with Parkinson’s disease. 

A study published in Nature Communications found that two key proteins, Lag3 and Aplp1, interact to facilitate alpha-synuclein toxicity. 

The researchers also found that using an anti-lag3 antibody disrupts this protein interaction and helps stop neurodegeneration in mice. If future research aligns with these findings, this could point to a potential way to stop the progression of Parkinson’s disease. 

The researchers used mice to look more at what is involved in the abnormal alpha-synuclein journey. They were able to confirm that two key proteins are involved: Aplp1 and Lag3. 

They found that the interaction between these two proteins contributes to the “binding, internalization, transmission, and toxicity of pathologic alpha-synuclein.” The findings also suggest that Aplp1 and Aplp1-Lag3 interaction contribute to alpha-synuclein’s cell-to-cell transmission. 

The research further supported that the genetic deletion of Aplp1 and Lag3 helped preserve dopaminergic neurons brain cells that release dopamine, the hormone whose production is impaired in Parkinson’s and eliminate behavior deficits from alpha-synuclein-preformed fibrils. The researchers investigated how using the Lag3 antibody 410C9 could help. They found that this antibody was able to disrupt the Aplp1-Lag-3 interaction. This helped prevent alpha-synuclein pathogenesis and transmission, which, in turn, helped prevent neurodegeneration and behavioral deficits.

By blocking the interaction between Aplp1 and Lag3, [we] found that anti-Lag3 antibody could prevent the spread of alpha-synuclein clumps in mouse models of Parkinson’s disease. This suggests that repurposing this FDA-approved drug could potentially slow or halt the progression of Parkinson’s disease in humans. This research has some key limitations, primarily in that testing something in mice differs from testing something in people. 

The researchers were also limited by the nature of their specific work, the procedures they used, and the effectiveness of using the type of mice they used in this research. 

The study authors also acknowledge that Aplp1 could promote Lag3’s action through something other than direct interaction, so more research is required in this area. They also want to look more at the physiological role of Aplp1 and Lag 3 and how these proteins may work with additional cell types. 

There are opportunities for future research in this area, which could ultimately lead to better outcomes for people with Parkinson’s disease. Parkinson’s disease impacts people in different ways. The disease has motor and nonmotor symptoms as we know now.

The motor symptoms cause tremors, rigidity, bradykinesia slowness of movement, and falling. These symptoms can severely affect daily activities and independence. Falling is most often the cause of death.