Open AccessGranulocyte-Colony Stimulating Factor Attenuates Oligomeric Amyloid β Neurotoxicity by Activation of Neprilysin
Author(s) -
Yukiko Doi,
Hideyuki Takeuchi,
Hideaki Mizoguchi,
Kazuya Fukumoto,
Hiroshi Horiuchi,
Shijie Jin,
Jun Koyama,
Bijay Parajuli,
Yoshifumi Sonobe,
Tetsuya Mizuno,
Akio Suzumura
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0103458
Subject(s) - neprilysin , neuroprotection , neurotoxicity , granulocyte colony stimulating factor , thiorphan , neurogenesis , enkephalinase , chemistry , pharmacology , microbiology and biotechnology , biology , medicine , biochemistry , enzyme , toxicity , receptor , chemotherapy , enkephalin , opioid
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.