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.

MicroRNA-181c Ameliorates Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats

“…It is well known that proper activation of NMDA receptors promotes neuronal survival and synaptic plasticity, while excessive NMDA receptors activation or inhibition leads to neurological disorders [51]. Overload of intracellular Ca 2+ induced by excessive NMDA receptor activation is directly linked to the activation of intracellular events responsible for cell death [52].…”

Advances in clinical neurology through the journal “Neurological Sciences” (2015–2016)

“…Vitamin D deficiency presents a greater risk for ApoEe4 non-carrier AD patients than for e4 carriers [107]. Nmethyl-D-aspartate receptors (NMDARs) play a pivotal role in the synaptic transmission and synaptic plasticity thought to underlie learning and memory and have been recently implicated in Alzheimer's disease [108]. Retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) has been evaluated and correlated with cognitive impairment, but further studies are needed to optimize the utility of this method as an ocular biomarker in AD [109].…”

Stem Cell Therapy: A Prospective Treatment for Alzheimer's Disease

“…In recent findings, the importance of glial cells and intercellular binding proteins in shaping the external environments of neurons have been suggested. The decline of microglia, astrocytes and oligodendrocytes that support the neuronal networks in the CNS through immune, nutritional and homeostatic mechanisms are correlated with the neuroinflammatory biochemistry of AD 4142. Additionally, the deterioration of central binding proteins between neurons such as Slitrk and LAR-RPTP contributes to the widespread neuronal loss 434445.…”