Unraveling a Key Player in Parkinson’s Disease: The Role of FAM171A2

Parkinson’s Disease (PD) is a complex neurological disorder, and scientists are constantly working to understand its underlying mechanisms. A critical aspect of PD involves the buildup and spread of a protein called alpha-synuclein (α-syn), which forms harmful clumps called fibrils. A recent study has shed light on this process, identifying a gene called FAM171A2 as a potential key player. Think of it like this: if α-syn fibrils are the villains causing trouble in the brain, FAM171A2 might be the doorway letting them in.

Here’s a breakdown of the exciting findings:

• FAM171A2 and Parkinson’s Risk: Research suggests that FAM171A2 is a risk gene for PD. This means variations in this gene could increase a person’s likelihood of developing the disease.
• Promoting Harmful Buildup: When FAM171A2 levels are high, it seems to encourage brain cells to take in more α-syn fibrils. This increased uptake worsens the spread of these toxic clumps and contributes to neuronal damage.
• Protective Effects of Lowering FAM171A2: Interestingly, when the researchers reduced FAM171A2 levels in neurons, it had a protective effect. This suggests that blocking FAM171A2 activity could be a potential therapeutic strategy.
• How Does it Work? The study revealed that a specific part of FAM171A2 interacts with the tail end of α-syn. This interaction is much stronger with the harmful α-syn fibrils than with the normal form of the protein – over 1000 times stronger, in fact! It’s like a lock and key mechanism where FAM171A2 acts as the lock, specifically designed for the harmful α-syn fibril key.
• A Potential Blocker: The researchers also identified a drug called bemcentinib that effectively blocks the interaction between FAM171A2 and α-syn fibrils. This discovery opens up exciting possibilities for developing new treatments for PD. Bemcentinib was tested in cells and mice, further strengthening the potential of this approach.

What does this all mean?

This research points to FAM171A2 as a potential new therapeutic target for Parkinson’s disease. By understanding how this gene contributes to the spread of toxic α-syn fibrils, scientists may be able to develop drugs that block its action, potentially slowing or even halting the progression of this debilitating disease. This exciting breakthrough offers hope for new and improved treatments for Parkinson’s in the future.