Postsynaptic receptors for amyloid-β oligomers as mediators of neuronal damage in Alzheimer’s disease
- Centro de Envejecimiento y Regeneración, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
The neurotoxic effect of amyloid-β peptide (Aβ) 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 Aβ receptors in neurons, and is still no clear why the Aβ oligomers only affect the excitatory synapses. Aβ 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 Aβ. In the present review we will document the interaction between Aβ 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 α7-nicotinic acetylcholine receptor. We conclude that several Aβ oligomers receptors exist at the excitatory synapse, which could be the responsible for the neurotoxic effect described for the Aβ oligomers. The characterization of the interaction between Aβ receptors and Aβ oligomers could help to understand the source of the neurologic damage observed in the brain of the Alzheimer’s disease patients.
Keywords: Aβ oligomers, postsynaptic receptors, neuroligin-1, synaptotoxicity, Alzheimer’s disease
Citation: Dinamarca MC, Ríos JA and Inestrosa NC (2012) Postsynaptic receptors for amyloid-β oligomers as mediators of neuronal damage in Alzheimer’s disease. Front. Physio. 3:464. doi: 10.3389/fphys.2012.00464
Received: 20 August 2012; Accepted: 22 November 2012;
Published online: 20 December 2012.
Copyright: © 2012 Dinamarca, Ríos and Inestrosa. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Nibaldo C. Inestrosa, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Centro de Envejecimiento y Regeneración, Pontificia Universidad Católica de Chile, Alameda 340, P.O. Box 114-D, Santiago, Chile. e-mail: firstname.lastname@example.org
†Present address: Margarita C. Dinamarca, Department of Pharmacological Sciences, University of Milan, Milan, Italy.