p(HGNCGENEFAMILY:"Glutamate ionotropic receptor NMDA type subunits")

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Name

Glutamate ionotropic receptor NMDA type subunits

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hgnc.genefamily

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20181015

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https://raw.githubusercontent.com/pharmacome/terminology/3074b85b858455d8eeb76cfcdef685ced19bbe11/external/hgnc.genefamily-names.belns

This file encodes the article Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function by Albuquerque et al, 2009

This file encodes the article Activation of M1 and M4 muscarinic receptors as potential treatments for Alzheimer’s disease and schizophrenia by Choi et al, 2014

The neuroactive properties of KYNA have long been attributed to the inhibition of NMDA receptors (329). Electrophysiological studies, however, have demonstrated that physiologically relevant concentrations of KYNA block alpha7 nAChR activity noncompetitively and voltage independently (210). PubMed:19126755

Thus, in brains from patients with AD and in neurons responding to exogenously applied Abeta, there is a reduction in expression of nAChR subunits, especially alpha4, alpha7, beta4, and possibly alpha3. Although AD may also involve changes in expression of other ligand-gated ion channels— for example, the expression of NMDA receptors (Bi and Sze, 2002; Jacob et al., 2007), alpha-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid receptors (Jacob et al., 2007), and beta3 GABA receptor subunits are all reduced (Mizukami et al., 1998)—there is abundant evidence of a loss of nAChR subunits in AD possibly caused by the actions of Abeta. PubMed:19293145

N-methyl-D-aspartate (NMDA) receptors play a critical role in regulating synaptic plasticity, and disrupted NMDA-receptor neurotransmission is thought to underlie the cognitive deficits observed in numerous psychiatric diseases. PubMed:24511233

M1 mAChRs have been demonstrated to potentiate NMDA-receptor signaling in the hippocampus and cortex,48,49 brain areas intimately associated with learning and memory. In addition, M1 KO mice displayed reduced hippocampal long-term potentiation, a mechanism heavily implicated in learning and memory. Behaviorally, M1 KO animals display deficits in several medial prefrontal cortex-dependent cognitive tasks, including non-matching-to- sample, win-shift radial arm maze, and social discrimination tasks. PubMed:24511233

Another early allosteric agonist, TBPB (1-(1’-(2-methylbenzyl) -1,4’-bipiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-1), also exhibited impressive selectivity for M1 mAChRs and potentiated NMDA receptor currents in CA1 hippocampal cells. PubMed:24511233

Only five drugs (Figure 1) have been approved by the U. S. Food and Drug Administration (FDA), four of which are cholinesterase inhibitors (tacrine, 15 donepezil, 16 rivastigmine 17 and galantamine 18 ) and one of which is a N-methyl-D-aspartate (NMDA) receptor antagonist (memantine 19 ). a N-methyl-D-aspartate (NMDA) receptor antagonist (memantine 19 ). These pharmacological agents have had limited effect in improving the cognitive function of AD patients and do not slow the progression of the disease. Clinical studies have shown that these agents temporarily stabilize cognitive impairment and help to maintain global function, delaying the need for patient palliative care by only a few month PubMed:30444369

There is evidence that anandamide is produced by postsynaptic neurons in response to elevated intracellular Ca2+ levels. For instance, concomitant activation of alpha7 nAChRs and NMDA receptors triggers the production of anandamine in postsynaptic neurons (448). Anandamine, then, functions as a retrograde messenger and regulates synaptic transmission by interacting with specific receptors in the presynaptic neurons/terminals (498). PubMed:19126755

N-methyl-D-aspartate (NMDA) receptors play a critical role in regulating synaptic plasticity, and disrupted NMDA-receptor neurotransmission is thought to underlie the cognitive deficits observed in numerous psychiatric diseases. PubMed:24511233

N-methyl-D-aspartate (NMDA) receptors play a critical role in regulating synaptic plasticity, and disrupted NMDA-receptor neurotransmission is thought to underlie the cognitive deficits observed in numerous psychiatric diseases. PubMed:24511233