{"doi":"10.3233/rnn-1998-00048","title":"Glumate Receptor Dysfunction and Alzheimer's Disease","abstract":"<jats:p>In this article we review the hypothesis that impaired function of the N-methyl-Daspartate (NMDA) glutamate receptor system may be an important mechanism for understanding the pathophysiology of Alzheimer's disease (AD). We propose a two stage process, the first involving amyloidopathy, oxidative stress and/or energy metabolic disturbances promoting neuronal sensitivity to glutamate-induced excitotoxic injury to an extent that even normal amounts of Glu become excitotoxic. As a consequence, NMDA receptor-bearing neurons (and their NMDA receptors) are deleted from critical corticolimbic brain circuits, which leaves these circuits in an NMDA receptor hypofunctional (NRHypo) state. In the second stage this NRHypo state results in the disinhibition of a complicated neural circuitry that leads to widespread neurodegeneration in corticolimbic areas, consquent neurofibrillary tangle formation and cognitive decline. We propose that certain pharmacological methodes which have been found to protect against NRHypo-induced neurodegeneration in animal brain might be useful treatments for AD.</jats:p>","journal":"Restorative Neurology and Neuroscience","year":1998,"id":637857,"datarank":0.5606504427425053,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"self_citation_contribution":0.5606504427425053,"citation_network_contribution":0.0,"self_endowment_contribution":0.5606504427425053,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":290776,"name":"David F. Wozniak","orcid":"0000-0003-3301-740X","position":1,"is_corresponding":false},{"id":524276,"name":"Nuri B. Farber","orcid":"0000-0003-3178-1877","position":2,"is_corresponding":false},{"id":1656417,"name":"John W. Olney","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Glumate Receptor Dysfunction and Alzheimer's Disease","abstract":"<jats:p>In this article we review the hypothesis that impaired function of the N-methyl-Daspartate (NMDA) glutamate receptor system may be an important mechanism for understanding the pathophysiology of Alzheimer's disease (AD). We propose a two stage process, the first involving amyloidopathy, oxidative stress and/or energy metabolic disturbances promoting neuronal sensitivity to glutamate-induced excitotoxic injury to an extent that even normal amounts of Glu become excitotoxic. As a consequence, NMDA receptor-bearing neurons (and their NMDA receptors) are deleted from critical corticolimbic brain circuits, which leaves these circuits in an NMDA receptor hypofunctional (NRHypo) state. In the second stage this NRHypo state results in the disinhibition of a complicated neural circuitry that leads to widespread neurodegeneration in corticolimbic areas, consquent neurofibrillary tangle formation and cognitive decline. We propose that certain pharmacological methodes which have been found to protect against NRHypo-induced neurodegeneration in animal brain might be useful treatments for AD.</jats:p>","is_dataset_classified":null,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12671289","pmcid":null,"openalex_id":"https://openalex.org/W184092676","authors":[],"funders":[],"total_grants":0,"fwci":0.4655,"citation_percentile":0.51159687,"influential_citations":0,"citation_trend":[{"year":2013,"count":1},{"year":2014,"count":1},{"year":2015,"count":4},{"year":2016,"count":2},{"year":2017,"count":1},{"year":2018,"count":1},{"year":2020,"count":2}],"oa_status":"closed","license":"https://journals.sagepub.com/page/policies/text-and-data-mining-license","oa_locations":[{"url":"https://journals.sagepub.com/doi/pdf/10.3233/RNN-1998-00048","host_type":"publisher"},{"url":"https://doi.org/10.3233/rnn-1998-00048","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12671289","host_type":"repository"}],"fields_of_study":["Neuroscience and Neuropharmacology Research","Alzheimer's disease research and treatments","Tryptophan and brain disorders"],"mesh_terms":[],"keywords":["Neuroscience","Neurodegeneration","NMDA receptor","Glutamate receptor","Excitotoxicity","Alzheimer's disease","Memantine","Disinhibition","Receptor","Disease","Psychology","Biology","Medicine","Internal medicine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T19:38:44.032732Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}