Lie D Chichung, Song Hongjun, Colamarino Sophia A, Ming Guo-li, Gage Fred H
Laboratory of Genetics, The Salk Institute, La Jolla, California 92037, USA.
Annu Rev Pharmacol Toxicol. 2004;44:399-421. doi: 10.1146/annurev.pharmtox.44.101802.121631.
New cells are continuously generated from immature proliferating cells throughout adulthood in many organs, thereby contributing to the integrity of the tissue under physiological conditions and to repair following injury. In contrast, repair mechanisms in the adult central nervous system (CNS) have long been thought to be very limited. However, recent findings have clearly demonstrated that in restricted areas of the mammalian brain, new functional neurons are constantly generated from neural stem cells throughout life. Moreover, stem cells with the potential to give rise to new neurons reside in many different regions of the adult CNS. These findings raise the possibility that endogenous neural stem cells can be mobilized to replace dying neurons in neurodegenerative diseases. Indeed, recent reports have provided evidence that, in some injury models, limited neuronal replacement occurs in the CNS. Here, we summarize our current understanding of the mechanisms controlling adult neurogenesis and discuss their implications for the development of new strategies for the treatment of neurodegenerative diseases.
在成年期,许多器官中未成熟的增殖细胞会持续产生新细胞,从而在生理条件下维持组织的完整性,并在损伤后参与修复过程。相比之下,长期以来人们一直认为成体中枢神经系统(CNS)的修复机制非常有限。然而,最近的研究结果清楚地表明,在哺乳动物大脑的特定区域,新的功能性神经元在整个生命过程中不断由神经干细胞产生。此外,具有产生新神经元潜力的干细胞存在于成体CNS的许多不同区域。这些发现增加了内源性神经干细胞可被动员起来替代神经退行性疾病中死亡神经元的可能性。事实上,最近的报告已经提供证据表明,在一些损伤模型中,CNS中会发生有限的神经元替代。在此,我们总结了目前对控制成体神经发生机制的理解,并讨论了它们对开发神经退行性疾病新治疗策略的意义。