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

Drews, Anna; Flint, Jennie; Shivji, Nadia; Jönsson, Peter LU ; Wirthensohn, David; De Genst, Erwin; Vincke, Cécile; Muyldermans, Serge; Dobson, Chris and Klenerman, David (2016) In Scientific Reports 6.
Abstract

Local delivery of amyloid beta oligomers from the tip of a nanopipette, controlled over the cell surface, has been used to deliver physiological picomolar 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... (More)

Local delivery of amyloid beta oligomers from the tip of a nanopipette, controlled over the cell surface, has been used to deliver physiological picomolar 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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
6
publisher
Nature Publishing Group
external identifiers
  • scopus:84984706229
  • wos:000381831300001
ISSN
2045-2322
DOI
10.1038/srep31910
language
English
LU publication?
yes
id
8339fb1c-5aac-4df3-aed8-4631f5bfceb4
date added to LUP
2016-12-02 12:58:08
date last changed
2017-11-19 04:35:25
@article{8339fb1c-5aac-4df3-aed8-4631f5bfceb4,
  abstract     = {<p>Local delivery of amyloid beta oligomers from the tip of a nanopipette, controlled over the cell surface, has been used to deliver physiological picomolar 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.</p>},
  articleno    = {31910},
  author       = {Drews, Anna and Flint, Jennie and Shivji, Nadia and Jönsson, Peter and Wirthensohn, David and De Genst, Erwin and Vincke, Cécile and Muyldermans, Serge and Dobson, Chris and Klenerman, David},
  issn         = {2045-2322},
  language     = {eng},
  month        = {08},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Individual aggregates of amyloid beta induce temporary calcium influx through the cell membrane of neuronal cells},
  url          = {http://dx.doi.org/10.1038/srep31910},
  volume       = {6},
  year         = {2016},
}