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The Role of Hyperexcitability in Gliomagenesis
Authors:Eric A. Goethe  Benjamin Deneen  Jeffrey Noebels  Ganesh Rao
Affiliation:1.Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA;2.Department of Cancer Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA;3.Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
Abstract:Glioblastoma is the most common malignant primary brain tumor. Recent studies have demonstrated that excitatory or activity-dependent signaling—both synaptic and non-synaptic—contribute to the progression of glioblastoma. Glutamatergic receptors may be stimulated via neuron–tumor synapses or release of glutamate by the tumor itself. Ion currents generated by these receptors directly alter the structure of membrane adhesion molecules and cytoskeletal proteins to promote migratory behavior. Additionally, the hyperexcitable milieu surrounding glioma increases the rate at which tumor cells proliferate and drive recurrent disease. Inhibition of excitatory signaling has shown to effectively reduce its pro-migratory and -proliferative effects.
Keywords:glioma   glioblastoma   tumor microenvironment   hyperexcitability   neuroglial synapse   glutamate   neuroligin-3
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