Abstract 1513 Zfra activates Hyal-2+ Z cells to induce expansion of neurons and neural stem cells to suppress neurodegeneration

Knockout Wwox-/- mice exhibit rapid aggregation of a brain protein cascade, commencing with TRAPPC6AΔ, TIAF1, and SH3GLB2, followed by tau and amyloid β within 2 weeks after birth. Zfra4-10 peptide restores memory loss in 9-month-old triple-transgenic mice for Alzheimer's disease (3xTg-AD) by halting the protein aggregation. Here, we determined how Zfra4-10 works. Circulating Zfra4-10, when polymerized, was sequestered in the spleen for months to consistently activate spleen memory CD3- CD19- Hyal-2+ Z cells to block pentylenetetrazol (PTZ)-induced seizures in mice, by preventing neuronal loss, reducing inflammatory microglia and astrocytes, and enhancing locomotion.