A target-based approach has been used to develop novel drugs in many therapeutic fields. However, this
approach remains suboptimal for drug discovery in brain disorders because the target identification in a brain disorder
requires a hierarchical integration from in vitro cellular and functional tissue studies to animal models that sustain
neuronal and glial complexity. Although glial cells comprise over half of the brain and play important roles in brain
function and disease, the intracellular signaling of glial cells remains essentially unexplored. This is because the lack of
optimal strategy to selectively activate or deactivate glial signaling has made it difficult to study glial roles. The recent
development of approaches using mouse models and enabling the selective activation of cell signaling could be used to
assess the role of glial cells in physiology and disease. This review presents how glial G- protein signaling contributes to
brain disorders and how the role of glia is investigated.
Keywords: Gq-DREADD (designer receptor exclusively activated by designer drug), glial cells, G-protein coupled receptors,
proteomics, neuronal disorder, tissue culture.
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