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

ABSTRACT:

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.

Methods

Oligomeric amyloid beta (oAβ) or tau (oTau) were applied to hippocampal neurons ± NVS-PAK1-1, a selective PAK1 inhibitor. NVS-PAK1-1 was orally administered to 5xFAD mice. The effects of NVS-PAK1-1 treatment on PAK1 activity, spine density, and the proteome were assessed using phospho-PAK1 (pPAK1) western blotting, Golgi staining, and mass spectrometry for proteomic analyses.

Results

NVS-PAK1-1 prevented oAβ and oTau-induced spine loss in vitro. In 5xFAD mice, NVS-PAK1-1 demonstrate

SUBMITTER: Yang T 

PROVIDER: S-EPMC12741935 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature