Molecular Double Agent: Protein 'Eato' Offers Unexpected Protection for the Brain

Researchers at Cornell University have uncovered a fascinating new role for the protein Eato in fruit flies—a discovery that could have significant implications for understanding and treating human neurodegenerative diseases like Alzheimer's and Parkinson's. Traditionally known in mammals for its role in lipid transport within brain cells, Eato has now been shown to perform a dual function: safeguarding neurons from destruction and aiding phagocytes (the brain’s cleanup cells) in identifying and removing damaged neurons.

The study involved experiments with Drosophila, commonly used in genetic research because of their biological similarity to humans. The team found that when Eato was absent from neurons, those cells did not survive—not because the neurons tore themselves apart, but because phagocytes were triggered to attack and digest them prematurely. This process was linked to a fatty molecule called phosphatidylserine (PS), which acts as an "eat-me" signal on the surface of stressed or dying neurons. Normally, Eato helps hide this signal on healthy neurons, preventing unnecessary phagocyte activation.

Without Eato, PS flips to the cell exterior too early, causing healthy neurons to be mistakenly identified as damaged and leading to their removal. Interestingly, removing the PS signal from neurons with Eato deficiency prevented degeneration, highlighting a potential target for therapy.

The findings shed light on the complex regulation of neuron health and the immune response in the brain. Since Eato belongs to the ABCA family of membrane proteins responsible for lipid regulation, this research also connects to known genetic factors in Alzheimer’s disease, such as ABCA1 and ABCA7. With Alzheimer’s being a leading cause of dementia and a major health concern worldwide—costing hundreds of billions annually—the potential to modulate PS exposure and phagocyte activity offers promising avenues for future interventions.

Lead researcher Chun Han emphasized that the dual role of Eato is surprising and differs from related proteins, opening up new research directions. Targeting the mechanisms governing PS signaling and phagocyte recognition could help prevent the loss of healthy neurons in neurodegenerative conditions. Overall, this study marks a significant step toward understanding how lipid transport proteins influence brain health and disease.

Published in Science Advances, this research not only deepens our knowledge of neuronal protection but also paves the way for innovative treatments aimed at halting or reversing neurodegeneration. Other contributors to this groundbreaking work include Bei Wang, Ankita Sarkar, Zixian Huang, Nicolas Vergara Ruiz, Ann T. Yeung, and Rachael Chen from Cornell University’s Weill Institute for Cell and Molecular Biology.