PAK1 inhibitor NVS-PAK1-1 preserves dendritic spines in amyloid/tau exposed neurons and 5xFAD mice

https://dx.doi.org/10.1002/alz.71033
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Tao Yang, Hasi Huhe, Sean-Paul Williams, Sukhneet Kaur, Yeonglong Albert Ay, Zachary W Davis-Gilbert, Gregory A Cary, Carolyn Paisie, Robert R Butler, Jesse Wiley, Ranjita Betarbet, Haian Fu, Duc Duong, Nicholas T Seyfried, Karina Leal, Gregory W Carter, Aled Edwards, Allan I Levey, Jacob L Capener, David H Drewry, Mohammad A Hossain, Hans J Oh, Alison D Axtman, Stacey J Sukoff Rizzo, Frank M Longo, Emory‐Sage‐SGC‐Jax TREAT‐AD Center,
INTRODUCTION: Synaptic spine loss in Alzheimer's disease (AD) contributes to cognitive decline. p21-activated kinase 1 (PAK1), a regulator of spine integrity, is aberrantly activated in AD. We investigated whether PAK1 inhibition might preserve dendritic spines in vitro and in vivo.