Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that mediate the majority of excitatory neurotransmission. iGluRs are gated by glutamate, where upon glutamate binding, they open their ion channels to enable cation influx into post-synaptic neurons, initiating signal transduction. The structural mechanism of iGluR gating by glutamate has been extensively studied in the context of positive allosteric modulators (PAMs).
View Article and Find Full Text PDFBackground: Vaccination against influenza has proven to reduce influenza-caused hospital entries, treatment times in intensive care units and hospitalisation costs for treating people with Diabetes Mellitus (DM). Despite the existing influenza vaccination recommendations for all persons with DM, in Spain, vaccination hesitancy remains substantial, and vaccination rates lag behind target. We aimed to assess predictors for influenza vaccination uptake and reasons for non-adherence among individuals with DM.
View Article and Find Full Text PDFMany animals exchange chemicals during courtship and mating. In some amphibians, sexual chemical communication is mediated by pheromones produced in male breeding glands that are transferred to the female's nostrils during mating. This has been mostly studied in salamanders, despite frogs having similar glands and courtship behaviours suggestive of chemical communication.
View Article and Find Full Text PDFMemantine is an US Food and Drug Administration (FDA) approved drug that selectively inhibits NMDA-subtype ionotropic glutamate receptors (NMDARs) for treatment of dementia and Alzheimer's. NMDARs enable calcium influx into neurons and are critical for normal brain function. However, increasing evidence shows that calcium influx in neurological diseases is augmented by calcium-permeable AMPA-subtype ionotropic glutamate receptors (AMPARs).
View Article and Find Full Text PDFExcitatory neurotransmission is principally mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-subtype ionotropic glutamate receptors (AMPARs). Negative allosteric modulators are therapeutic candidates that inhibit AMPAR activation and can compete with positive modulators to control AMPAR function through unresolved mechanisms. Here we show that allosteric inhibition pushes AMPARs into a distinct state that prevents both activation and positive allosteric modulation.
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