Abstract
In Alzheimer’s disease (AD), early synaptic dysfunction is associated with the increased oligomeric amyloid-beta peptide, which causes NMDAR-dependent synaptic depression and spine elimination. Memantine, low-affinity NMDAR channel blocker, has been used in the treatment of moderate to severe AD. However, clear evidence is still deficient in demonstrating the underlying mechanisms and a relationship between NMDARs dysfunction and AD. This review focuses on not only changes in expression of different NMDAR subunits, but also some unconventional modes of NMDAR action.
Highlights
Alzheimer’s disease (AD) is an age-related neurodegenerative disease
N-methyl-D-aspartate receptors (NMDARs) function was potentiated in microglia from the APPSw,Ind transgenic mice, indicating that the NCS1–NMDAR interaction is relevant for receptor function in the microglia of the AD mouse model (Franco et al, 2018)
One might predict that, compared to GluN1/GluN2B diheteromers, GluN1/GluN2B/GluN3A triheteromers might be less sensitive to lower concentrations of ifenprodil where GluN2B specificity is greater, as previous studies have shown that the magnitude of ifenprodil block depends on the number of GluN2B subunits contained within the NMDAR complex (Hatton and Paoletti, 2005)
Summary
Alzheimer’s disease (AD) is an age-related neurodegenerative disease This disorder is characterized by global cognitive dysfunction, especially memory loss, behavior and personality changes. AD progression has been associated with a gradual damage in function and structure in the hippocampus and neocortex, the vulnerable brain areas used for memory and cognition (Mota et al, 2014). The. Role of NMDA Receptors in AD pathological level of Ca2+ signaling leads to gradual loss of synaptic function and ultimate neuronal cell death, which correlates clinically with the progressive decline in cognition/memory and the development of pathological neural anatomy seen in AD patients. Taking into account the fact that extrasynaptic GluN2B-containing NMDARs have been associated with excitotoxicity in AD (Hardingham and Bading, 2010), the use of a selective GluN2B subunit antagonists might be an interesting strategy to prevent synaptic dysfunction in AD
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