| 会長招聘講演 |
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| 3L2
Gliomagenesis and GRIA2-An Integrated vertical study from Gene to Disease
Ishiuchi Shogo
Department of Neurosurgery, Graduate School of Medicine, University of the Ryukyus
Glioblastoma multiforme is the most notorious bran cancer, and affects preferentialy adult with more than 60 years of age. Neural stem cells and/or glial progenitors of the subventrilar zone（SVZ）are suspicious of origin of gliomas. Recent studies unravelled that human and other mammalian brains contain a pool of neural stem cells throughout the life. Glutamate-mediated signaling plays a pivotal role for developmental and adult neurogenesis through ionotoropic glutamate receptor such as NMDA receptors（NMDAR）, and AMPA receptors（AMPAR）. Although NMDAR activation is essential for neuronal birth and survival at the developmetal stage,in contrast,adult neurogenesis is stimulated by blockade of NMDAR. AMPARs participate in fast neuronal transmission. GluA2 encoded by GRIA2 gene, a subunit of AMPA receptors, is the determinant of Ca2+-permeability by downregulation of GRIA2, an impairment of RNA editing processes, and trafficking of GluA1 encoded by GRIA1. We have previously shown that activation of Ca2+-permeable AMPA-type glutamate receptors facilitates the migration and proliferation of human glioblastoma cells（Nat med. 2012, J Neurosci 2007, J Neurosurg 2014）. Furthermore, there is accumulating evidence that Ca2+-permeable AMPA receptors more widely play important roles in various human cancers than originally thought. We have found that blockade of NMDAR in the dentate gyrus of hippocampus restored disturbance of neurogenesis which was induced by radiotherapy. Adult hippocampal cell derived from GRIA2KO mice induced gliomagenesis indicating important role of GRIA2 in gliomagenesis. Regulation of NMDAR and AMPAR using specific inhibitors will be a novel attractive therapy for this devasting disease. | | | |
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