Signaling cascades implicated in muscarinic regulation of proliferation of neural stem and progenitor cells.
Muscarinic acetylcholine receptors (mAChRs) belong to the G-protein-coupled receptor superfamily that transduces signals through multiple intracellular signaling cascades to regulate a wide variety of physiological responses. Recently, it has been discovered that subtypes of mAChRs are expressed in proliferative neuroepithelial cells of the ventricular zone and in basic fibroblast growth factor-expanded neural stem and progenitor cell cultures. Activation of the mAChRs by ACh or its analogue carbachol leads to increased DNA synthesis and neurogenesis. The mitogenic effects of muscarinic agonists are likely mediated via mAChR-activated multisignaling pathways. The exact intracellular mechanisms underlying mAChR-modulated DNA synthesis and neurogenesis are not fully understood. However, several pathways through Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C, c-Src and Ca(2+) signaling have been shown to play roles in this dynamic process. These novel signaling cascades may improve our understanding of the intracellular mechanisms underlying mAChR-stimulated neural progenitor proliferation and provide insights for therapeutic drug development.
Ma
Wu
W
Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, Washington DC, USA.
Li
Bing-Sheng
BS
Zhang
Lei
L
Pant
Harish C
HC
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*
D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C