Amyloid-β Protein Oligomer at Low Nanomolar Concentrations Activates Microglia and Induces Microglial Neurotoxicity

Izumi Maezawa,Pavel I Zimin,Heike Wulff,Lee-Way Jin

doi:10.1074/jbc.m110.135244

Izumi Maezawa, Pavel I Zimin + Show 2 more

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https://doi.org/10.1074/jbc.m110.135244

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Abstract

Amyloid-β Protein Oligomer at Low Nanomolar Concentrations Activates Microglia and Induces Microglial Neurotoxicity

Highlights

A␤,2 a hydrophobic protein derived from proteolytic processing of the amyloid-␤ precursor protein, self-aggregates into amyloid fibrils and deposits as amyloid plaques, one of the
The indirect neurotoxicity was prevented by (i) doxycycline, an inhibitor of microglia activation; (ii) TRAM-34, a selective KCa3.1 blocker; and (iii) two inhibitors of inducible nitric oxide (NO) synthase, indicating that KCa3.1 activity and excessive NO release are required for as oligomers (A␤O)-induced microglial neurotoxicity
The mitogenic effect was confirmed by BrdUrd incorporation. Proliferation measured by both cell counting and BrdUrd followed a bell-shaped curve (Fig. 1, B and C), which is very similar to the previously reported chemotactic activity of soluble A␤ for macrophages/microglia that maximized at low nanomolar concentrations [30]

Summary

Introduction

A␤,2 a hydrophobic protein derived from proteolytic processing of the amyloid-␤ precursor protein, self-aggregates into amyloid fibrils and deposits as amyloid plaques, one of the. A␤O at low nanomolar concentrations, not neurotoxic, induced indirect, microglia-mediated damage to neurons in dissociated cultures and in organotypic hippocampal slices. A␤O at Low Nanomolar Concentrations Stimulates Microglia into a Distinct Activation Phenotype—Our A␤O preparations affected viability of cultured hippocampal neurons at concentrations above 100 nM, consistent with previously published results [22].

Results

Conclusion