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Front. Mol. Biosci. | doi: 10.3389/fmolb.2018.00106

Changes in serine racemase-dependent modulation of NMDA receptor: impact on physiological and pathological brain ageing

  • 1University of Caen Normandy, France
  • 2INSERM U1075 Université de Caen Normandie - Pôle des Formations et de Recherche en Santé, France

The N-methyl-D-Aspartate glutamate receptors (NMDARs) are pivotal for the functional and morphological plasticity that are required in neuronal networks for efficient brain activities and notably for cognitive-related abilities. Because NMDARs are heterogeneous in subunit composition and associated with multiple functional regulatory sites, their efficacy is under the tonic influence of numerous allosteric modulations, whose dysfunction generally represents the first step generating pathological states. Among the enzymatic candidates, serine racemase (SR) has recently gathered an increasing interest considering that it tightly regulates the production of D-serine, an amino acid now viewed as the main endogenous co-agonist necessary for NMDAR activation. Nowadays, SR deregulation is associated with a wide range of neurological and psychiatric diseases including schizophrenia, amyotrophic lateral sclerosis and depression. This review aims at compelling the most recent experimental evidences indicating that changes in SR-related modulation of NMDARs also govern opposite functional dysfunctions in physiological and pathological (Alzheimer’s disease) ageing that finally results in memory disabilities in both cases. It also highlights SR as a relevant alternative target for new pharmacological strategies aimed at preventing functional alterations and cognitive impairments linked to the ageing process.

Keywords: NMDA receptor, serine racemase, Ageing, Alzheimer ' s disease, d-serine, long term potentiation (LTP), Glutamate

Received: 21 Sep 2018; Accepted: 09 Nov 2018.

Edited by:

Andrea Mozzarelli, Università degli Studi di Parma, Italy

Reviewed by:

Ashok Kumar, University of Florida, United States
Silvia Sacchi, Università degli Studi dell'Insubria, Italy  

Copyright: © 2018 Billard. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Jean-Marie Billard, University of Caen Normandy, Caen, 14032, Lower Normandy, France, jean-marie.billard@inserm.fr