Granulocyte-Colony Stimulating Factor Attenuates Oligomeric Amyloid beta Neurotoxicity by Activation of Neprilysin

作者：Doi Yukiko; Takeuchi Hideyuki; Mizoguchi Hiroyuki; Fukumoto Kazuya; Horiuchi Hiroshi; Jin Shijie; Kawanokuchi Jun; Parajuli Bijay; Sonobe Yoshifumi; Mizuno Tetsuya^*; Suzumura Akio

来源：PLos One, 2014, 9(7): e103458.

DOI：10.1371/journal.pone.0103458

Soluble oligomeric amyloid beta (oA beta) 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 and drives neurogenesis. Here we show that G-CSF attenuated oA beta neurotoxicity through the enhancement of the enzymatic activity of A beta-degrading enzyme neprilysin (NEP) in neurons he 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 A beta in APP/PS1 transgenic mice. Thus, we propose that G-CSF may be a possible therapeutic strategy against AD.

• 出版日期2014-7-25