Choi Sung S, Lee Sang-Rae, Lee Hong J
Biomedical Research Institute, Chung-Ang University College of Medicine, Seoul 156-756, Korea.
Curr Alzheimer Res. 2016;13(4):419-27. doi: 10.2174/156720501304160314162812.
Neurogenesis is maintained in both neonatal and adult brain, although it is dramatically reduced in aged neurogenic brain region such as the subgranular layer and subventricular zone of the dentate gyrus (DG). Astrocytes play important roles for survival and maintenance of neurons as well as maintenance of neurogenic niche in quiescent state. Aβ can induce astrocyte activation which give rise to produce reactive oxygen species (ROS) and cytotoxic cytokines and chemokines, and subsequently induce neuronal death. Unfortunately, the current therapeutic medicines have been limited to reduce the symptoms and delay the pathogenesis of Alzheimer's disease (AD), but not to cure it. Stem cells enhance neurogenesis and Aβ clearing as well as improved cognitive impairment. Neurotrophins and growth factors which are produced from both stem cells and astrocytes also have neuroprotective effects via neurogenesis. Secreted factors from both astrocytes and neural stem cells also are influenced in neurogenesis and neuron survival in neurodegenerative diseases. Transplanted stem cells overexpressing neurogenic factors may be an effective and therapeutic tool to enhance neurogenesis for AD.
神经发生在新生儿和成年大脑中均有维持,尽管在老年神经源性脑区,如齿状回颗粒下层和脑室下区,神经发生显著减少。星形胶质细胞对神经元的存活和维持以及静止状态下神经源性微环境的维持起着重要作用。β淀粉样蛋白(Aβ)可诱导星形胶质细胞活化,进而产生活性氧(ROS)、细胞毒性细胞因子和趋化因子,随后诱导神经元死亡。遗憾的是,目前的治疗药物仅限于减轻阿尔茨海默病(AD)的症状和延缓其发病机制,而无法治愈该病。干细胞可增强神经发生、清除Aβ以及改善认知障碍。干细胞和星形胶质细胞产生的神经营养因子和生长因子也通过神经发生发挥神经保护作用。星形胶质细胞和神经干细胞分泌的因子在神经退行性疾病的神经发生和神经元存活中也会受到影响。过表达神经源性因子的移植干细胞可能是增强AD神经发生的一种有效治疗工具。