We found that low OXR1 levels in humans correlate with #Alzheimers, so we drove tau-induced toxicity in fly eyes, to see if we could rescue it with OXR1/retromer. Overexpression of OXR1 or retromer genes prevented this toxicity. Lots more to come from this, so stay tuned! Happy to discuss more 😊

We next wanted to see if enhancing the retromer rescues brain degeneration. Not only did it reduce degeneration in brains of flies that had lost OXR1, but it improved age-related #neurodegeneration as well.

We next found that OXR1 is expressed with proteins in the endolysosomal network. By staining fly brains, we found that loss of OXR1 causes loss of proteins in the #retromer complex, like VPS35. The retromer takes cargo from endosomes and traffics them for reuse, as opposed to breakdown.

We screened in flies for genes undergoing dietary restriction (DR) to find new regulators of longevity. A top candidate gene was called mustard, or OXR1 in humans. We found that DR upregulates OXR1 and is necessary for lifespan extension by DR. Overexpression of OXR1 extended lifespan in flies!