Dinamarca_2015_Biochem.Biophys.Res.Commun_466_66

Amyloid-beta oligomers (Abetao) 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 Abetao receptors. We recently found that Abetao interact with the soluble N-terminal fragment of neuroligin-1 (NL-1). We report here that Abetao 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 Abetao in a complex with GluN2B-containing NMDA receptors. Additionally, the soluble fragment of NL-1 was used as a scavenger for Abetao. Field excitatory postsynaptic potentials indicate that fragments of NL-1 protect hippocampal neurons from the impairment induced by Abetao. To our knowledge, this is the first report of the interaction between this extracellular fragment of NL-1 and Abetao, strongly suggest that NL-1 facilitates the targeting of Abetao to the postsynaptic regions of excitatory synapses.