Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation
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BioMed Central
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Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation Rodrigo R Resende*1,2 and Avishek Adhikari3 Address: 1Department of Physics, Institute of Exact Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil, 2Institute of Learning and Research Santa Casa of BH (IEPSC – BH), Belo Horizonte, Brazil and 3Department of Biological Sciences, Columbia University, New York, NY, 10027, USA Email: Rodrigo R Resende* - [email protected]; Avishek Adhikari - [email protected] * Corresponding author
Published: 27 August 2009 Cell Communication and Signaling 2009, 7:20
doi:10.1186/1478-811X-7-20
Received: 8 June 2009 Accepted: 27 August 2009
This article is available from: http://www.biosignaling.com/content/7/1/20 © 2009 Resende and Adhikari; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Acetylcholine (ACh) has been shown to modulate neuronal differentiation during early development. Both muscarinic and nicotinic acetylcholine receptors (AChRs) regulate a wide variety of physiological responses, including apoptosis, cellular proliferation and neuronal differentiation. However, the intracellular mechanisms underlying these effects of AChR signaling are not fully understood. It is known that activation of AChRs increase cellular proliferation and neurogenesis and that regulation of intracellular calcium through AChRs may underlie the many functions of ACh. Intriguingly, activation of diverse signaling molecules such as Ras-mitogenactivated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C and c-Src is modulated by AChRs. Here we discuss the roles of ACh in neuronal differentiation, cell proliferation and apoptosis. We also discuss the pathways involved in these processes, as well as the effects of novel endogenous AChRs agonists and strategies to enhance neuronal-differentiation of stem and neural progenitor cells. Further understanding of the intracellular mechanisms underlying AChR signaling may provide insights for novel therapeutic strategies, as abnormal AChR activity is present in many diseases.
Introduction Acetylcholine (ACh) is an ancient signaling molecule, [1] and is present in both prokaryotes and eukaryotes [2-4]. Although ACh has been extensively studied for its role as a neurotransmitter, it also has autocrine functions [5] in diverse cell types. ACh has been shown to promote cytoskeleton organization, cellular proliferation, differentiation and apoptosis [2-4,6-8] throughout development [2,3,9]. Intriguingly nAChR signaling pathways have been preserved throughout evolution [10], suggesting that they have critical functions. We shall attempt to discuss the physiology of ACh as well as ACh's relevant downstream
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