Group III metabotropic glutamate receptors as promising targets for neuroprotective therapy: Particular emphasis on the role of mGlu4 and mGlu7 receptors

Domin, Helena

doi:10.1016/j.pbb.2022.173452

Cited by 13 publications

(5 citation statements)

References 94 publications

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“…The different and heterogeneous locations of mGluRs in the CNS could provide individualized treatment options by selectively targeting different receptor subtypes. Because of its heterogeneity, the mGluR7 family of receptors are promising targets for neuroprotective therapy ( Domin, 2022 ). In vivo and in vitro studies in mice have also revealed that the activation of Group III mGluRs exerts neuroprotective effects, partly through homeostasis of glutamate levels ( Bruno et al, 2000 ).…”

Section: Discussionmentioning

confidence: 99%

GRM7 deficiency, from excitotoxicity and neuroinflammation to neurodegeneration: Systematic review of GRM7 deficient patients

Zaki-Dizaji,

Abazari,

Razzaghi

et al. 2024

Brain, Behavior, & Immunity - Health

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Section: Discussionmentioning

confidence: 99%

GRM7 deficiency, from excitotoxicity and neuroinflammation to neurodegeneration: Systematic review of GRM7 deficient patients

Zaki-Dizaji,

Abazari,

Razzaghi

et al. 2024

Brain, Behavior, & Immunity - Health

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“…Group III mGluR ligands have many properties that have attracted attention as targets for neurological disease therapy [9,33]. For example, the mGlu4 positive allosteric modulator, PHCCC, and the mGlu7 allosteric agonist AMN082 provided relief from akinesia in a reserpine-treated rat model of Parkinson's disease, which the authors believed most likely reflected the inhibition of excess glutamate release [34].…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Modulation of Excitotoxicity through the Combined Use of NMDA Receptor Inhibition and Group III mGlu Activation Reduces TMT-Induced Neurodegeneration in the Rat Hippocampus

Першина

Chernomorets

Fedorov

et al. 2023

IJMS

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We studied the neuroprotective properties of the non-competitive NMDA receptor antagonist memantine, in combination with a positive allosteric modulator of metabotropic glutamate receptors of Group III, VU 0422288. The treatment was started 48 h after the injection of neurotoxic agent trimethyltin (TMT) at 7.5 mg/kg. Three weeks after TMT injection, functional and morphological changes in a rat hippocampus were evaluated, including the expression level of genes characterizing glutamate transmission and neuroinflammation, animal behavior, and hippocampal cell morphology. Significant neuronal cell death occurred in the CA3 and CA4 regions, and to a lesser extent, in the CA1 and CA2 regions. The death of neurons in the CA1 field was significantly reduced in animals with a combined use of memantine and VU 0422288. In the hippocampus of these animals, the level of expression of genes characterizing glutamatergic synaptic transmission (Grin2b, Gria1, EAAT2) did not differ from the level in control animals, as well as the expression of genes characterizing neuroinflammation (IL1b, TGF beta 1, Aif1, and GFAP). However, the expression of genes characterizing neuroinflammation was markedly increased in the hippocampus of animals treated with memantine or VU 0422288 alone after TMT. The results of immunohistochemical studies confirmed a significant activation of microglia in the hippocampus three weeks after TMT injection. In contrast to the hilus, microglia in the CA1 region had an increase in rod-like cells. Moreover, in the CA1 field of the hippocampus of the animals of the MEM + VU group, the amount of such microglia was close to the control. Thus, the short-term modulation of glutamatergic synaptic transmission by memantine and subsequent activation of Group III mGluR significantly affected the dynamics of neurodegeneration in the hippocampus.

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“…The group III mGluR agonist ACPT-I exerts neuroprotective effects in ischemic stroke and improves post-ischemic gait impairment [163]. ACPT-I exerts similar effects in spontaneously hypertensive rats (SHR) after MCAO/R [132,164]. mGluR6 is not expressed in the brain but only in the retina [165].…”

Section: Group III Mglursmentioning

confidence: 99%

Exploring the Neuroprotective Effects of Lithium in Ischemic Stroke: A literature review

Wang,

Lu,

Shi

et al. 2024

Int. J. Med. Sci.

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Ischemic stroke ranks among the foremost clinical causes of mortality and disability, instigating neuronal degeneration, fatalities, and various sequelae. While standard treatments, such as intravenous thrombolysis and endovascular thrombectomy, prove effective, they come with limitations. Hence, there is a compelling need to develop neuroprotective agents capable of improving the functional outcomes of the nervous system. Numerous preclinical studies have demonstrated that lithium can act in multiple molecular pathways, including glycogen synthase kinase 3(GSK-3), the Wnt signaling pathway, the mitogen-activated protein kinase (MAPK)/ extracellular signal-regulated kinase (ERK) signaling pathway, brain-derived neurotrophic factor (BDNF), mammalian target of rapamycin (mTOR), and glutamate receptors. Through these pathways, lithium has been shown to affect inflammation, autophagy, apoptosis, ferroptosis, excitotoxicity, and other pathological processes, thereby improving central nervous system (CNS) damage caused by ischemic stroke. Despite these promising preclinical findings, the number of clinical trials exploring lithium's efficacy remains limited. Additional trials are imperative to thoroughly ascertain the effectiveness and safety of lithium in clinical settings. This review delineates the mechanisms underpinning lithium's neuroprotective capabilities in the context of ischemic stroke. It elucidates the intricate interplay between these mechanisms and sheds light on the involvement of mitochondrial dysfunction and inflammatory markers in the pathophysiology of ischemic stroke. Furthermore, the review offers directions for future research, thereby advancing the understanding of the potential therapeutic utility of lithium and establishing a theoretical foundation for its clinical application.

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Group III metabotropic glutamate receptors as promising targets for neuroprotective therapy: Particular emphasis on the role of mGlu4 and mGlu7 receptors

Cited by 13 publications

References 94 publications

GRM7 deficiency, from excitotoxicity and neuroinflammation to neurodegeneration: Systematic review of GRM7 deficient patients

GRM7 deficiency, from excitotoxicity and neuroinflammation to neurodegeneration: Systematic review of GRM7 deficient patients

Pharmacological Modulation of Excitotoxicity through the Combined Use of NMDA Receptor Inhibition and Group III mGlu Activation Reduces TMT-Induced Neurodegeneration in the Rat Hippocampus

Exploring the Neuroprotective Effects of Lithium in Ischemic Stroke: A literature review

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