Attenuation of amyloid β (Aβ)-induced inhibition of phosphatidylinositol 4-kinase activity by Aβ fragments, Aβ20–29 and Aβ31–35

Abstract

We previously reported that pathophysiological concentrations of amyloid β protein (Aβ25–35, 0.1–10 nM) directly inhibited type II phosphatidylinositol 4-kinase (PI4KII) activity in neuronal plasma membranes, which resulted in the enhanced glutamate neurotoxicity. In the present study, we examined the effects of Aβ fragments, Aβ20–29 and Aβ31–35, on the 10 nM Aβ25–35- or Aβ1–42-induced inhibition of PI4KII activity. Both of the peptide fragments recovered the inhibition of rat brain plasma membrane PI4KII activity over the concentration range of 0.1–5 nM. Such protection by the Aβ fragments was observed in the 10 nM Aβ25–35-induced inhibition of recombinant human PI4KII, suggesting that these Aβ fragments blocked the inhibition on PI4KII molecule. The Aβ25–35-induced enhancement of glutamate neurotoxicity was also completely inhibited in the presence of these fragments. Thus, Aβ20–29 and Aβ31–35 ameliorated the Aβ-enhanced glutamate neurotoxicity probably through attenuation of Aβ-induced inhibition of PI4KII activity.