Unraveling a Parkinson’s Mystery: Could FAM171A2 Hold the Key?

Parkinson’s disease is a complex neurological disorder, and scientists are constantly working to understand its intricate mechanisms. A major player in this disease is a protein called alpha-synuclein (α-syn). When this protein clumps together into harmful “fibrils,” it can spread through the brain, damaging nerve cells along the way. But how do these fibrils get inside the nerve cells in the first place? New research suggests a fascinating culprit: a gene called FAM171A2.

Here’s what this exciting research reveals:

• FAM171A2: A potential gateway for α-syn fibrils: This gene appears to play a crucial role in letting α-syn fibrils enter neurons. Think of it like a doorway that the fibrils use to get inside. When FAM171A2 is overactive, it seems to swing this doorway wide open, allowing more fibrils to enter and wreak havoc.
• Boosting FAM171A2 worsens Parkinson’s-like effects: Experiments show that increasing FAM171A2 levels leads to increased uptake of α-syn fibrils, making the damaging effects of α-syn even worse. This further strengthens the idea that FAM171A2 is a key player in the disease process.
• Silencing FAM171A2 offers protection: Conversely, when the researchers lowered FAM171A2 levels in neurons, they saw a protective effect against α-syn damage. This suggests that blocking FAM171A2 could be a promising therapeutic strategy.
• A sticky situation: The researchers discovered how FAM171A2 and α-syn interact. A specific part of FAM171A2 (its extracellular domain 1) binds strongly to the tail end of α-syn fibrils, much like two magnets attracting each other. This interaction is remarkably selective for the harmful fibrils over the normal form of α-syn.
• Bemcentinib: A potential blocker: The study also identified a drug called bemcentinib that can effectively block the interaction between FAM171A2 and α-syn fibrils. This exciting discovery opens up the possibility of using bemcentinib or similar drugs to slow or even halt the progression of Parkinson’s disease.

This groundbreaking research identifies FAM171A2 as a potential therapeutic target for Parkinson’s disease. By interfering with the interaction between FAM171A2 and α-syn fibrils, we may be able to develop new treatments to slow or prevent the progression of this devastating disease. This is a significant step forward in our understanding of Parkinson’s and offers hope for future therapies. Further research is underway to explore the full potential of this discovery.