Department of Physics, Institute of Exact Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
Cell Commun Signal. 2009 Aug 27;7:20. doi: 10.1186/1478-811X-7-20.
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-mitogen-activated 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.
乙酰胆碱 (ACh) 已被证明可在早期发育过程中调节神经元分化。毒蕈碱和烟碱型乙酰胆碱受体 (AChR) 调节多种生理反应，包括细胞凋亡、细胞增殖和神经元分化。然而，AChR 信号转导产生这些影响的细胞内机制尚不完全清楚。已知 AChR 的激活可增加细胞增殖和神经发生，并且通过 AChR 调节细胞内钙可能是 ACh 发挥许多功能的基础。有趣的是，各种信号分子的激活，如 Ras-丝裂原活化蛋白激酶、磷脂酰肌醇 3-激酶-Akt、蛋白激酶 C 和 c-Src，都受 AChR 的调节。在这里，我们讨论了 ACh 在神经元分化、细胞增殖和细胞凋亡中的作用。我们还讨论了这些过程中涉及的途径，以及新型内源性 AChR 激动剂的作用和增强干细胞和神经祖细胞的神经元分化的策略。进一步了解 AChR 信号转导的细胞内机制可能为新型治疗策略提供思路，因为许多疾病中都存在异常的 AChR 活性。
