Department of Molecular Cardiology, NB50, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA.
Pharmacol Rev. 2012 Jul;64(3):645-75. doi: 10.1124/pr.111.004762. Epub 2012 May 18.
The importance of adult neurogenesis has only recently been accepted, resulting in a completely new field of investigation within stem cell biology. The regulation and functional significance of adult neurogenesis is currently an area of highly active research. G-protein-coupled receptors (GPCRs) have emerged as potential modulators of adult neurogenesis. GPCRs represent a class of proteins with significant clinical importance, because approximately 30% of all modern therapeutic treatments target these receptors. GPCRs bind to a large class of neurotransmitters and neuromodulators such as norepinephrine, dopamine, and serotonin. Besides their typical role in cellular communication, GPCRs are expressed on adult neural stem cells and their progenitors that relay specific signals to regulate the neurogenic process. This review summarizes the field of adult neurogenesis and its methods and specifies the roles of various GPCRs and their signal transduction pathways that are involved in the regulation of adult neural stem cells and their progenitors. Current evidence supporting adult neurogenesis as a model for self-repair in neuropathologic conditions, adult neural stem cell therapeutic strategies, and potential avenues for GPCR-based therapeutics are also discussed.
成人神经发生的重要性最近才被接受，这导致了干细胞生物学中一个全新的研究领域的出现。成人神经发生的调节和功能意义目前是一个高度活跃的研究领域。G 蛋白偶联受体 (GPCR) 已成为成人神经发生的潜在调节剂。GPCR 是一类具有重要临床意义的蛋白质，因为大约 30%的现代治疗方法都针对这些受体。GPCR 结合了一大类神经递质和神经调质，如去甲肾上腺素、多巴胺和血清素。除了在细胞通讯中的典型作用外，GPCR 还在成年神经干细胞及其祖细胞上表达，这些细胞将特定信号传递到调节神经发生过程。这篇综述总结了成人神经发生及其方法领域，并具体说明了各种 GPCR 及其信号转导途径在调节成年神经干细胞及其祖细胞中的作用。还讨论了支持成人神经发生作为神经病理学疾病自我修复模型、成年神经干细胞治疗策略以及基于 GPCR 的治疗的潜在途径的现有证据。
