Contribution of TRPC Channels in Neuronal Excitotoxicity Associated With Neurodegenerative Disease and Ischemic Stroke
The seven canonical members of transient receptor potential (TRPC) proteins form cation channels that evoke membrane depolarization and intracellular calcium concentration ([Ca2+]i) rise, which are not only important for regulating cell function but their deregulation can also lead to cell damage. R...
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Frontiers Media S.A.
2021-01-01
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Series: | Frontiers in Cell and Developmental Biology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2020.618663/full |
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doaj-690c32be34764b418f6b4070138f35b9 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jaepyo Jeon Fan Bu Guanghua Sun Jin-Bin Tian Shun-Ming Ting Jun Li Jaroslaw Aronowski Lutz Birnbaumer Lutz Birnbaumer Lutz Birnbaumer Marc Freichel Marc Freichel Michael X. Zhu |
spellingShingle |
Jaepyo Jeon Fan Bu Guanghua Sun Jin-Bin Tian Shun-Ming Ting Jun Li Jaroslaw Aronowski Lutz Birnbaumer Lutz Birnbaumer Lutz Birnbaumer Marc Freichel Marc Freichel Michael X. Zhu Contribution of TRPC Channels in Neuronal Excitotoxicity Associated With Neurodegenerative Disease and Ischemic Stroke Frontiers in Cell and Developmental Biology neurological disease TRPC4 knockout calcium neuroprotection neurodegeneration neuronal death |
author_facet |
Jaepyo Jeon Fan Bu Guanghua Sun Jin-Bin Tian Shun-Ming Ting Jun Li Jaroslaw Aronowski Lutz Birnbaumer Lutz Birnbaumer Lutz Birnbaumer Marc Freichel Marc Freichel Michael X. Zhu |
author_sort |
Jaepyo Jeon |
title |
Contribution of TRPC Channels in Neuronal Excitotoxicity Associated With Neurodegenerative Disease and Ischemic Stroke |
title_short |
Contribution of TRPC Channels in Neuronal Excitotoxicity Associated With Neurodegenerative Disease and Ischemic Stroke |
title_full |
Contribution of TRPC Channels in Neuronal Excitotoxicity Associated With Neurodegenerative Disease and Ischemic Stroke |
title_fullStr |
Contribution of TRPC Channels in Neuronal Excitotoxicity Associated With Neurodegenerative Disease and Ischemic Stroke |
title_full_unstemmed |
Contribution of TRPC Channels in Neuronal Excitotoxicity Associated With Neurodegenerative Disease and Ischemic Stroke |
title_sort |
contribution of trpc channels in neuronal excitotoxicity associated with neurodegenerative disease and ischemic stroke |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-01-01 |
description |
The seven canonical members of transient receptor potential (TRPC) proteins form cation channels that evoke membrane depolarization and intracellular calcium concentration ([Ca2+]i) rise, which are not only important for regulating cell function but their deregulation can also lead to cell damage. Recent studies have implicated complex roles of TRPC channels in neurodegenerative diseases including ischemic stroke. Brain ischemia reduces oxygen and glucose supply to neurons, i.e., Oxygen and Glucose Deprivation (OGD), resulting in [Ca2+]i elevation, ion dyshomeostasis, and excitotoxicity, which are also common in many forms of neurodegenerative diseases. Although ionotropic glutamate receptors, e.g., N-methyl-D-aspartate receptors, are well established to play roles in excitotoxicity, the contribution of metabotropic glutamate receptors and their downstream effectors, i.e., TRPC channels, should not be neglected. Here, we summarize the current findings about contributions of TRPC channels in neurodegenerative diseases, with a focus on OGD-induced neuronal death and rodent models of cerebral ischemia/reperfusion. TRPC channels play both detrimental and protective roles to neurodegeneration depending on the TRPC subtype and specific pathological conditions involved. When illustrated the mechanisms by which TRPC channels are involved in neuronal survival or death seem differ greatly, implicating diverse and complex regulation. We provide our own data showing that TRPC1/C4/C5, especially TRPC4, may be generally detrimental in OGD and cerebral ischemia/reperfusion. We propose that although TRPC channels significantly contribute to ischemic neuronal death, detailed mechanisms and specific roles of TRPC subtypes in brain injury at different stages of ischemia/reperfusion and in different brain regions need to be carefully and systematically investigated. |
topic |
neurological disease TRPC4 knockout calcium neuroprotection neurodegeneration neuronal death |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2020.618663/full |
work_keys_str_mv |
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doaj-690c32be34764b418f6b4070138f35b92021-01-08T05:57:13ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-01-01810.3389/fcell.2020.618663618663Contribution of TRPC Channels in Neuronal Excitotoxicity Associated With Neurodegenerative Disease and Ischemic StrokeJaepyo Jeon0Fan Bu1Guanghua Sun2Jin-Bin Tian3Shun-Ming Ting4Jun Li5Jaroslaw Aronowski6Lutz Birnbaumer7Lutz Birnbaumer8Lutz Birnbaumer9Marc Freichel10Marc Freichel11Michael X. Zhu12Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United StatesDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United StatesDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United StatesDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United StatesDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United StatesDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United StatesDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United StatesInstitute for Biomedical Research (BIOMED UCA-CONICET), Buenos Aires, ArgentinaSchool of Medical Sciences, Catholic University of Argentina (UCA), Buenos Aires, ArgentinaNeurobiology Laboratory, National Institute of Environmental Health Sciences, Durham, NC, United StatesDepartment of Pharmacology, Heidelberg University, Heidelberg, GermanyDZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Heidelberg, GermanyDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United StatesThe seven canonical members of transient receptor potential (TRPC) proteins form cation channels that evoke membrane depolarization and intracellular calcium concentration ([Ca2+]i) rise, which are not only important for regulating cell function but their deregulation can also lead to cell damage. Recent studies have implicated complex roles of TRPC channels in neurodegenerative diseases including ischemic stroke. Brain ischemia reduces oxygen and glucose supply to neurons, i.e., Oxygen and Glucose Deprivation (OGD), resulting in [Ca2+]i elevation, ion dyshomeostasis, and excitotoxicity, which are also common in many forms of neurodegenerative diseases. Although ionotropic glutamate receptors, e.g., N-methyl-D-aspartate receptors, are well established to play roles in excitotoxicity, the contribution of metabotropic glutamate receptors and their downstream effectors, i.e., TRPC channels, should not be neglected. Here, we summarize the current findings about contributions of TRPC channels in neurodegenerative diseases, with a focus on OGD-induced neuronal death and rodent models of cerebral ischemia/reperfusion. TRPC channels play both detrimental and protective roles to neurodegeneration depending on the TRPC subtype and specific pathological conditions involved. When illustrated the mechanisms by which TRPC channels are involved in neuronal survival or death seem differ greatly, implicating diverse and complex regulation. We provide our own data showing that TRPC1/C4/C5, especially TRPC4, may be generally detrimental in OGD and cerebral ischemia/reperfusion. We propose that although TRPC channels significantly contribute to ischemic neuronal death, detailed mechanisms and specific roles of TRPC subtypes in brain injury at different stages of ischemia/reperfusion and in different brain regions need to be carefully and systematically investigated.https://www.frontiersin.org/articles/10.3389/fcell.2020.618663/fullneurological diseaseTRPC4 knockoutcalciumneuroprotectionneurodegenerationneuronal death |