Dinamarca_2012_Front.Physiol_3_464

The neurotoxic effect of amyloid-beta peptide (Abeta) over the central synapses has been described and is reflected in the decrease of some postsynaptic excitatory proteins, the alteration in the number and morphology of the dendritic spines, and a decrease in long-term potentiation. Many studies has been carried out to identify the putative Abeta receptors in neurons, and is still no clear why the Abeta oligomers only affect the excitatory synapses. Abeta oligomers bind to neurite and preferentially to the postsynaptic region, where the postsynaptic protein-95 (PSD-95) is present in the glutamatergic synapse, and interacts directly with the N-methyl-D-aspartate receptor (NMDAR) and neuroligin (NL). NL is a postsynaptic protein which binds to the presynaptic protein, neurexin to form a heterophilic adhesion complex, the disruption of this interaction affects the integrity of the synaptic contact. Structurally, NL has an extracellular domain homolog to acetylcholinesterase, the first synaptic protein that was found to interact with Abeta. In the present review we will document the interaction between Abeta and the extracellular domain of NL-1 at the excitatory synapse, as well as the interaction with other postsynaptic components, including the glutamatergic receptors (NMDA and mGluR5), the prion protein, the neurotrophin receptor, and the alpha7-nicotinic acetylcholine receptor. We conclude that several Abeta oligomers receptors exist at the excitatory synapse, which could be the responsible for the neurotoxic effect described for the Abeta oligomers. The characterization of the interaction between Abeta receptors and Abeta oligomers could help to understand the source of the neurologic damage observed in the brain of the Alzheimer's disease patients.