Individual aggregates of amyloid beta induce temporary calcium influx through the cell membrane of neuronal cells;

Anna Drews, Jennie Flint, Nadia Shivji, Peter Jönsson, David Wirthensohn, Erwin De Genst, Cecile Vincke, Serge Muyldermans, Christopher M. Dobson, David Klenerman

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40 Citations (Scopus)
153 Downloads (Pure)

Abstract

Local delivery of amyloid beta oligomers from the tip of a nanopipette, controlled over the cell surface, has been used to deliver physiological pico molar oligomer concentrations to primary astrocytes or neurons. Calcium influx was observed when as few as 2000 oligomers were delivered to the cell surface. When the dosing of oligomers was stopped the intracellular calcium returned to basal levels or below. Calcium influx was prevented by the presence in the pipette of the extracellular chaperone clusterin, which is known to selectively bind oligomers, and by the presence a specific nanobody to amyloid beta. These data are consistent with individual oligomers larger than trimers inducing calcium entry as they cross the cell membrane, a result supported by imaging experiments in bilayers, and suggest that the initial molecular event that leads to neuronal damage does not involve any cellular receptors, in contrast to work performed at much higher oligomer concentrations.
Original languageEnglish
Article number31910
Number of pages12
JournalScientific Reports - Nature
Volume6
DOIs
Publication statusPublished - 24 Aug 2016

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