{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:45:21Z","timestamp":1789181121897,"version":"build-2803163510"},"reference-count":204,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ReST Therapeutics","award":["#0682"],"award-info":[{"award-number":["#0682"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>N-methyl-d-aspartate receptors (NMDARs) are the main class of ionotropic receptors for the excitatory neurotransmitter glutamate. They play a crucial role in the permeability of Ca2+ ions and excitatory neurotransmission in the brain. Being heteromeric receptors, they are composed of several subunits, including two obligatory GluN1 subunits (eight splice variants) and regulatory GluN2 (GluN2A~D) or GluN3 (GluN3A~B) subunits. Widely distributed in the brain, they regulate other neurotransmission systems and are therefore involved in essential functions such as synaptic transmission, learning and memory, plasticity, and excitotoxicity. The present review will detail the structure, composition, and localization of NMDARs, their role and regulation at the glutamatergic synapse, and their impact on cognitive processes and in neurodegenerative diseases (Alzheimer\u2019s, Huntington\u2019s, and Parkinson\u2019s disease). The pharmacology of different NMDAR antagonists and their therapeutic potentialities will be presented. In particular, a focus will be given on fluoroethylnormemantine (FENM), an investigational drug with very promising development as a neuroprotective agent in Alzheimer\u2019s disease, in complement to its reported efficacy as a tomography radiotracer for NMDARs and an anxiolytic drug in post-traumatic stress disorder.<\/jats:p>","DOI":"10.3390\/ijms25073733","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T13:45:01Z","timestamp":1711547101000},"page":"3733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Targeting N-Methyl-d-Aspartate Receptors in Neurodegenerative Diseases"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4639-2244","authenticated-orcid":false,"given":"Allison","family":"Carles","sequence":"first","affiliation":[{"name":"MMDN, University of Montpellier, EPHE, INSERM, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Freyssin","sequence":"additional","affiliation":[{"name":"MMDN, University of Montpellier, EPHE, INSERM, Montpellier, France"},{"name":"ReST Therapeutics, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Perin-Dureau","sequence":"additional","affiliation":[{"name":"ReST Therapeutics, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9762-8932","authenticated-orcid":false,"given":"Gilles","family":"Rubinstenn","sequence":"additional","affiliation":[{"name":"ReST Therapeutics, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4074-6793","authenticated-orcid":false,"given":"Tangui","family":"Maurice","sequence":"additional","affiliation":[{"name":"MMDN, University of Montpellier, EPHE, INSERM, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/0278-5846(88)90102-9","article-title":"Glutamate transmission and toxicity in Alzheimer\u2019s disease","volume":"12","author":"Greenamyre","year":"1988","journal-title":"Prog. 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