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Causes Of Alzheimer’s Disease
Published in Zaven S. Khachaturian, Teresa S. Radebaugh, Alzheimer’s Disease, 2019
Kainate receptors are very dense in hippocampus, and when several of these individuals died, the damage in hippocampus paralleled the distribution of kainate receptors. It is as yet unclear whether individuals who were exposed to the toxin but did not develop severe symptoms acutely will eventually develop similar problems as they age.
Glutamate Sensing in Plants
Published in Akula Ramakrishna, Victoria V. Roshchina, Neurotransmitters in Plants, 2018
Jesús Salvador López-Bucio, Homero Reyes de la Cruz, A. Arturo Guevara-García
Considering the ubiquitous presence of Glu and its receptors, it seems likely that glutamatergic systems (metabolism, release mechanisms, receptors, and transporters) are somehow involved in almost all aspects of normal brain development, function, and aging, as well as, in most neurological diseases (Danbolt, 2001). Mammalian iGluRs are subdivided into three types: R-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors, N-methyl-D-aspartic acid (NMDA) receptors, and kainate receptors (Kew et al., 2005; Featherstone, 2010). Fast information flow in the nervous system is thought to occur mostly via AMPA receptors. Kainate receptors, though found postsynaptically in some synapses, are (like mGluRs) also present on presynaptic terminal membranes, where they serve to autoregulate synaptic vesicle function and Glu secretion. NMDA receptors tend to remain open longer than AMPA or kainate receptors, allowing significant calcium influx. Thus, NMDA receptor activation can initiate intracellular calcium-dependent signaling cascades that lead to changes in gene expression and synaptic strength, which manifest for example in learning and memory (Kew et al., 2005; Featherstone, 2010). There is little or no biochemical conversion of Glu in the extracellular space, meaning that it is capable of continuously interacting with receptors until it diffuses away or is removed from the extracellular fluid by excitatory amino acid transporters (EAATs) (Danbolt, 2001; Featherstone, 2010).
Effects of Alcohol Abuse on Brain Neurochemistry
Published in John Brick, Handbook of the Medical Consequences of Alcohol and Drug Abuse, 2012
Until recently there has been much controversy regarding the effect of ethanol on kainate receptors. This was mainly due to the inability of researchers to pharmacologically isolate kainate receptors from other glutamate receptors. The few studies mentioned previously found that ethanol inhibited kainate receptor function in recombinant receptor systems. However, these findings only suggested such an effect was possible, as the characteristics of recombinant kainate receptors differ from endogenous receptors.
Progress in the development of kynurenine and quinoline-3-carboxamide-derived drugs
Published in Expert Opinion on Investigational Drugs, 2020
Further types of ionotropic glutamate receptors in the CNS are the AMPA and the kainate receptors. As kynurenines can alter glutamate levels by several mechanisms modifying both uptake and conversion, one would expect that under specific conditions, they have effects on these receptors as well. Indeed, KYNA is a competitive inhibitor of AMPA receptors at millimolar concentrations; in nanomolar to micromolar levels, however, KYNA induces their facilitation through allosteric modulation [6]. KYNA has also been reported to inhibit presynaptic α7nAChRs, and by doing so, to decrease presynaptic glutamate release and extracellular Gamma Amino Butyric Acid (GABA) levels [11,12]. However, as some of the later studies reported no such effects recently T.W. Stone reviewed published data on KYNA and α7nAChRs interactions and concluded that critical reevaluation of previous experimental results does not support the claim that KYNA is a ligand of α7nACh receptors [14].
A kainate receptor GluK4 deletion, protective against bipolar disorder, is associated with enhanced cognitive performance across diagnoses in the TwinsUK cohort
Published in The World Journal of Biological Psychiatry, 2019
Maria Koromina, Miles Flitton, Ian R. Mellor, Helen Miranda Knight
Kainate receptors are ionotropic glutamate receptors involved in cellular functions necessary for learning and memory, such as synaptic plasticity, long-term potentiation and neurotransmission (Bortolotto et al. 1999; Schmitz et al. 2003; Bortolotto et al. 2005; Lerma and Marques 2013; Sihra and Rodriguez-Moreno 2013; Sihra et al. 2014). They are composed of tetrameric combinations of five subunits (GluK1-GluK5; encoded by GRIK1-GRIK5) and modulated by auxiliary proteins Neto1 and Neto2 (Lerma et al. 2001; Jane et al. 2009; Traynelis et al. 2010; Han et al. 2016; Kristensen et al. 2016; Li et al. 2016). We have previously reported GRIK4/GluK4 as a breakpoint gene disrupted in a complex chromosomal rearrangement in a patient diagnosed with schizophrenia co-morbid with learning disability (Pickard et al. 2006, 2008). Subsequent case–control genetic studies led to the identification of a 14-base pair deletion variant (indel) (rs869187535) within the 3′ untranslated region of the gene which was negatively associated with bipolar disorder (Pickard et al. 2006; Knight et al. 2012).
The impact of perampanel and targeting AMPA transmission on anti-seizure drug discovery
Published in Expert Opinion on Drug Discovery, 2019
Simona Lattanzi, Pasquale Striano
Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are the main post-synaptic glutamate receptors to mediate the fast-synaptic excitatory neurotransmission and the fast component of the EPSP. Hypersensitivity, upregulation, and increased density of AMPA receptors have been demonstrated in hippocampal and neocortical tissues obtained from patients with epilepsy, and altered expression and phosphorylation of AMPA receptors have been pointed out in epileptogenesis. N-methyl-D-aspartate (NMDA) receptors need to be activated by depolarization and glutamate binding, contribute to a later and slower component of the EPSP, and are mostly involved in calcium-dependent responses underlying synaptic plasticity [6]. Finally, kainate receptors are the less frequently encountered type of ionotropic glutamate receptor. They are located at pre-synaptic level where regulate neurotransmitter release, and their role in the pathophysiology of epileptic activity has to be fully understood, yet.