Contribution of TRPC channels in neuronal excitotoxicity associated with neurodegenerative disease and ischemic stroke

• Autores: Jeon, Jaepyo; Bu, Fan; Sun, Guanghua; Tian, Jin-Bin; Ting, Shun-Ming; Li, Jun; Aronowski, Jaroslaw; Birnbaumer, Lutz; Freichel, Marc; Zhu, Michael X.
• Año de publicación: 2021
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Frontiers in cell and developmental biology. 2021, 8
• Materia: TRCP; FISIOPATOLOGÍA; ENFERMEDADES NEURODEGENERATIVAS; ACCIDENTE CEREBROVASCULAR; LESION CEREBRAL
• Institución: Pontificia Universidad Católica Argentina

Fil: Jeon, Jaepyo. Universidad deTexas. Centro de Ciencias de la Salud. Escuela de Medicina McGovern. Departamento de Biología Integrativa y Farmacología; Estados Unidos
Fil: Bu, Fan. Universidad deTexas. Centro de Ciencias de la Salud. Escuela de Medicina McGovern. Departamento de Neurología; Estados Unidos
Fil: Sun, Guanghua. Universidad deTexas. Centro de Ciencias de la Salud. Escuela de Medicina McGovern. Departamento de Neurología; Estados Unidos
Fil: Tian, Jin-Bin. Universidad deTexas. Centro de Ciencias de la Salud. Escuela de Medicina McGovern. Departamento de Biología Integrativa y Farmacología; Estados Unidos
Fil: Ting, Shun-Ming. Universidad deTexas. Centro de Ciencias de la Salud. Escuela de Medicina McGovern. Departamento de Neurología; Estados Unidos
Fil: Li, Jun. Universidad deTexas. Centro de Ciencias de la Salud. Escuela de Medicina McGovern. Departamento de Neurología; Estados Unidos
Fil: Aronowski, Jaroslaw. Universidad deTexas. Centro de Ciencias de la Salud. Escuela de Medicina McGovern. Departamento de Neurología; Estados Unidos
Fil: Birnbaumer, Lutz. Instituto Nacional de Ciencias de la Salud Ambiental. Laboratorio de neurobiología; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Freichel, Marc. Universidad de Heidelberg. Departamento de Farmacología; Alemania
Fil: Freichel, Marc. Centro Alemán de Investigación Cardiovascular; Alemania
Fil: Zhu, Michael X. Universidad deTexas. Centro de Ciencias de la Salud. Escuela de Medicina McGovern. Departamento de Biología Integrativa y Farmacología; Estados Unidos
Abstract: The seven canonical members of transient receptor potential (TRPC) proteins form cation channels that evoke membrane depolarization and intracellular calcium concentration ([Ca2C]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 [Ca2C]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.