The soluble extracellular fragment of neuroligin-1 targets Aβ oligomers to the postsynaptic region of excitatory synapses

Biochemical and Biophysical Research Communications
Margarita C DinamarcaNibaldo C Inestrosa

Abstract

Amyloid-β oligomers (Aβo) play a major role in the synaptic dysfunction of Alzheimer's disease (AD). Neuroligins are postsynaptic cell-adhesion molecules, that share an extracellular domain with high degree of similarity to acetylcholinesterase (AChE), one of the first putative Aβo receptors. We recently found that Aβo interact with the soluble N-terminal fragment of neuroligin-1 (NL-1). We report here that Aβo associate with NL-1 at excitatory hippocampal synapses, whereas almost no association was observed with neuroligin-2, an isoform present at inhibitory synapses. Studies using purified hippocampal postsynaptic densities indicate that NL-1 interacts with Aβo in a complex with GluN2B-containing NMDA receptors. Additionally, the soluble fragment of NL-1 was used as a scavenger for Aβo. Field excitatory postsynaptic potentials indicate that fragments of NL-1 protect hippocampal neurons from the impairment induced by Aβo. To our knowledge, this is the first report of the interaction between this extracellular fragment of NL-1 and Aβo, strongly suggest that NL-1 facilitates the targeting of Aβo to the postsynaptic regions of excitatory synapses.

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Citations

Feb 18, 2016·Molecular Neurobiology·Daniela VallejoNibaldo C Inestrosa
Jun 1, 2016·Neural Plasticity·Iryna Leshchyns'ka, Vladimir Sytnyk
Oct 14, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Edward J GoetzlJanice B Schwartz
Aug 29, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Edward J Goetzl
Mar 12, 2017·The Journal of Biological Chemistry·Jordano Brito-MoreiraSergio T Ferreira
Mar 24, 2017·Neural Plasticity·Viviana I TorresNibaldo C Inestrosa
May 2, 2018·Journal of Alzheimer's Disease : JAD·M Clara SellesSergio T Ferreira
Feb 2, 2021·Acta Neuropathologica Communications·Elena CamporesiBruno Becker
Dec 27, 2017·Current Opinion in Neurobiology·Aaron Katzman, Cristina M Alberini

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