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Reelin and apoE actions on signal transduction, synaptic function and memory formation

Published online by Cambridge University Press:  13 August 2009

Justin T. Rogers
Affiliation:
Department of Molecular Pharmacology and Physiology, Johnnie B Byrd Sr. Alzheimer's Center & Research Institute, University of South Florida, 4001 East Fletcher Ave., Tampa FL 33613, USA
Edwin J. Weeber*
Affiliation:
Department of Molecular Pharmacology and Physiology, Johnnie B Byrd Sr. Alzheimer's Center & Research Institute, University of South Florida, 4001 East Fletcher Ave., Tampa FL 33613, USA
*
Correspondence should be addressed to: Edwin J. Weeber, Department of Molecular Pharmacology and Physiology, Johnnie B Byrd Sr. Alzheimer's Center & Research Institute, University of South Florida, 4001 East Fletcher Ave., Tampa FL 33613, USA email: eweeber@health.usf.edu

Abstract

Low-density-lipoprotein receptors (LDLRs) are an evolutionarily ancient surface protein family with the ability to activate a diversity of extracellular signals across the cellular membrane in the adult central nervous system (CNS). Their intimate roles in modulating synaptic plasticity and their necessity in hippocampal-dependent learning and memory have only recently come to light. Two known LDLR ligands, specifically apolipoprotein E (apoE) and reelin, have been the most widely investigated in this regard. Most of our understanding of synaptic plasticity comes from investigation of both pre- and postsynaptic alterations. Therefore, it is interesting to note that neurons and glia that do not contribute to the synaptic junction in question can secrete signaling molecules that affect synaptic plasticity. Notably, reelin and apoE have been shown to modulate hippocampal long-term potentiation in general, and affect NMDA receptor and AMPA receptor regulation specifically. Furthermore, these receptors and signaling molecules have significant roles in neuronal degenerative diseases such as Alzheimer's disease. The recent production of recombinant proteins, knockout and transgenic mice for receptors and ligands and the development of human ApoE targeted replacement mice have significantly expanded our understanding of the roles LDLRs and their ligands have in certain disease states and the accompanying initiation of specific signaling pathways. This review describes the role LDLRs, apoE and reelin have in the regulation of hippocampal synaptic plasticity.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2009

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