Effect of the ROCK Inhibitor Fasudil on the Brain Proteomic Profile in the Tau Transgenic Mouse Model of Alzheimer's Disease

Overview

Journal Front Aging Neurosci

Specialty Geriatrics

Date 2024 Mar 5

PMID 38440100

Authors

Roberto Collu

Zheng Yin

Elisa Giunti

Sarah Daley

Mei Chen

Peter Morin

Richard Killick

Stephen T C Wong

Weiming Xia

Affiliations

Soon will be listed here.

Abstract

Introduction: The goal of this study is to explore the pharmacological potential of the amyloid-reducing vasodilator fasudil, a selective Ras homolog (Rho)-associated kinases (ROCK) inhibitor, in the P301S tau transgenic mouse model (Line PS19) of neurodegenerative tauopathy and Alzheimer's disease (AD).

Methods: We used LC-MS/MS, ELISA and bioinformatic approaches to investigate the effect of treatment with fasudil on the brain proteomic profile in PS19 tau transgenic mice. We also explored the efficacy of fasudil in reducing tau phosphorylation, and the potential beneficial and/or toxic effects of its administration in mice.

Results: Proteomic profiling of mice brains exposed to fasudil revealed the activation of the mitochondrial tricarboxylic acid (TCA) cycle and blood-brain barrier (BBB) gap junction metabolic pathways. We also observed a significant negative correlation between the brain levels of phosphorylated tau (pTau) at residue 396 and both fasudil and its metabolite hydroxyfasudil.

Conclusions: Our results provide evidence on the activation of proteins and pathways related to mitochondria and BBB functions by fasudil treatment and support its further development and therapeutic potential for AD.

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