title: Dysfunction of NMDA receptors in Alzheimer's disease.
abstract: N-methyl-D-aspartate receptors (NMDARs) play a pivotal role in the synaptic transmission and synaptic plasticity thought to underlie learning and memory. NMDARs activation has been recently implicated in Alzheimer's disease (AD) related to synaptic dysfunction. Synaptic NMDARs are neuroprotective, whereas overactivation of NMDARs located outside of the synapse cause loss of mitochondrial membrane potential and cell death. NMDARs dysfunction in the glutamatergic tripartite synapse, comprising presynaptic and postsynaptic neurons and glial cells, is directly involved in AD. This review discusses that both beta-amyloid (Aβ) and tau perturb synaptic functioning of the tripartite synapse, including alterations in glutamate release, astrocytic uptake, and receptor signaling. Particular emphasis is given to the role of NMDARs as a possible convergence point for Aβ and tau toxicity and possible reversible stages of the AD through preventive and/or disease-modifying therapeutic strategies.
authors.affiliation: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, 410013, Hunan, China.|Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, 410078, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, 410078, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, 410078, Hunan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, 410078, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, 410078, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, 410078, Hunan, China.
authors.forename: Peiyao
authors.initials: P
authors.lastname: Li
authors.affiliation: Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, 410078, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, 410078, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, 410078, Hunan, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Feng
authors.affiliation: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, 410013, Hunan, China. wuminghua554@aliyun.com.|Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, 410078, Hunan, China. wuminghua554@aliyun.com.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, 410078, Hunan, China. wuminghua554@aliyun.com.|Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, 410078, Hunan, China. wuminghua554@aliyun.com.
authors.forename: Minghua
authors.initials: M
authors.lastname: Wu
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D006801:Humans; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016194:Receptors, N-Methyl-D-Aspartate; D016875:tau Proteins
keywords: AD; Extrasynaptic; NMDA receptors; Synaptic transmission; Tripartite synapse