Epilepsy is a neurological disorder characterized by high morbidity,high recurrence,and drug resistance.Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy.Meta...Epilepsy is a neurological disorder characterized by high morbidity,high recurrence,and drug resistance.Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy.Metabotropic glutamate receptors(mGluRs)are G protein-coupled receptors activated by glutamate and are key regulators of neuronal and synaptic plasticity.Dysregulated mGluR signaling has been associated with various neurological disorders,and numerous studies have shown a close relationship between mGluRs expression/activity and the development of epilepsy.In this review,we first introduce the three groups of mGluRs and their associated signaling pathways.Then,we detail how these receptors influence epilepsy by describing the signaling cascades triggered by their activation and their neuroprotective or detrimental roles in epileptogenesis.In addition,strategies for pharmacological manipulation of these receptors during the treatment of epilepsy in experimental studies is also summarized.We hope that this review will provide a foundation for future studies on the development of mGluR-targeted antiepileptic drugs.展开更多
Cancer stem cells(CSCs),a minor subpopulation of tumor bulks with self-renewal and seeding capacity to generate new tumors,posit a significant challenge to develop effective and long-lasting anti-cancer therapies.The ...Cancer stem cells(CSCs),a minor subpopulation of tumor bulks with self-renewal and seeding capacity to generate new tumors,posit a significant challenge to develop effective and long-lasting anti-cancer therapies.The emergence of drug resistance appears upon failure of chemo-/radiation therapy to eradicate the CSCs,thereby leading to CSC-mediated clinical relapse.Accumulating evidence suggests that transcription factor SOX2,a master regulator of embryonic and induced pluripotent stem cells,drives cancer stemness,fuels tumor initiation,and contributes to tumor aggressiveness through major drug resistance mechanisms like epithelial-to-mesenchymal transition,ATP-binding cassette drug transporters,anti-apoptotic and/or pro-survival signaling,lineage plasticity,and evasion of immune surveillance.Gaining a better insight and comprehensive interrogation into the mechanistic basis of SOX2-mediated generation of CSCs and treatment failure might therefore lead to new therapeutic targets involving CSC-specific anti-cancer strategies.展开更多
基金supported by the Natural Science Foundation of Hunan Province,No.2021JJ30389(to JG)the Key Research and Development Program of Hunan Province of China,Nos.2022SK2042(to LL)and 2020SK2122(to ET)。
文摘Epilepsy is a neurological disorder characterized by high morbidity,high recurrence,and drug resistance.Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy.Metabotropic glutamate receptors(mGluRs)are G protein-coupled receptors activated by glutamate and are key regulators of neuronal and synaptic plasticity.Dysregulated mGluR signaling has been associated with various neurological disorders,and numerous studies have shown a close relationship between mGluRs expression/activity and the development of epilepsy.In this review,we first introduce the three groups of mGluRs and their associated signaling pathways.Then,we detail how these receptors influence epilepsy by describing the signaling cascades triggered by their activation and their neuroprotective or detrimental roles in epileptogenesis.In addition,strategies for pharmacological manipulation of these receptors during the treatment of epilepsy in experimental studies is also summarized.We hope that this review will provide a foundation for future studies on the development of mGluR-targeted antiepileptic drugs.
基金This work is supported by the National Key Scientific Program of China(2016YFA0100502)M.A.M.is a recipient of the CASTWAS President’s Fellowship.X.S.is a recipient of the 1000 Talents Plan Professorship for Young Talents(KJ2070000026).
文摘Cancer stem cells(CSCs),a minor subpopulation of tumor bulks with self-renewal and seeding capacity to generate new tumors,posit a significant challenge to develop effective and long-lasting anti-cancer therapies.The emergence of drug resistance appears upon failure of chemo-/radiation therapy to eradicate the CSCs,thereby leading to CSC-mediated clinical relapse.Accumulating evidence suggests that transcription factor SOX2,a master regulator of embryonic and induced pluripotent stem cells,drives cancer stemness,fuels tumor initiation,and contributes to tumor aggressiveness through major drug resistance mechanisms like epithelial-to-mesenchymal transition,ATP-binding cassette drug transporters,anti-apoptotic and/or pro-survival signaling,lineage plasticity,and evasion of immune surveillance.Gaining a better insight and comprehensive interrogation into the mechanistic basis of SOX2-mediated generation of CSCs and treatment failure might therefore lead to new therapeutic targets involving CSC-specific anti-cancer strategies.
