Granulocyte-colony Stimulating Factor Attenuates Oligomeric Amyloid β Neurotoxicity by Activation of Neprilysin

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Jul 26

PMID 25062013

Citations 5

Authors

Yukiko Doi

Hideyuki Takeuchi

Hiroyuki Mizoguchi

Kazuya Fukumoto

Hiroshi Horiuchi

Shijie Jin

Jun Kawanokuchi

Bijay Parajuli

Yoshifumi Sonobe

Tetsuya Mizuno

Akio Suzumura

Affiliations

Soon will be listed here.

Abstract

Soluble oligomeric amyloid β (oAβ) causes synaptic dysfunction and neuronal cell death, which are involved in the pathogenesis of Alzheimer's disease (AD). The hematopoietic growth factor granulocyte-colony stimulating factor (G-CSF) is expressed in the central nervous system (CNS) and drives neurogenesis. Here we show that G-CSF attenuated oAβ neurotoxicity through the enhancement of the enzymatic activity of Aβ-degrading enzyme neprilysin (NEP) in neurons, while the NEP inhibitor thiorphan abolished the neuroprotection. Inhibition of MEK5/ERK5, a major downstream effector of G-CSF signaling, also ablated neuroprotective effect of G-CSF. Furthermore, intracerebroventricular administration of G-CSF enhanced NEP enzymatic activity and clearance of Aβ in APP/PS1 transgenic mice. Thus, we propose that G-CSF may be a possible therapeutic strategy against AD.

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