Granulocyte-Colony Stimulating Factor Attenuates Oligomeric Amyloid Beta Neurotoxicity By Activation Of Neprilysin

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.