In our recent study, we explored how neurons cope with toxic, misfolded proteins—an especially important question since these cells can’t simply divide to replace damaged ones. We found that, beyond its traditional role in degrading unwanted proteins, the autophagy pathway can also export harmful protein variants. Specifically, we showed that the Alzheimer-associated ubiquitin variant UBB+1 is recognized by the autophagy adaptor p62, packaged into vesicles, and secreted from cells. When p62 is missing, UBB+1 instead accumulates inside neurons, increasing proteotoxic stress. These findings identify UBB+1 as a new cargo for secretory autophagy and broaden our understanding of how cells manage protein quality to maintain neuronal health.
Well done to Ajay R. Wagh for a wonderful and insightful research!