Gao Chong, Wang Qi, Chung Sookja K, Shen Jiangang
School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Hong Kong, Hong Kong SAR, China.
Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Neurochem Int. 2017 Jun;106:24-36. doi: 10.1016/j.neuint.2017.02.001. Epub 2017 Feb 7.
Metabolic disorders like diabetes and obesity are commonly companied with neurological diseases and psychiatric disorders. Accumulating evidences indicated that cellular metabolic factors affect adult neurogenesis and have modulating effects on neurodegenerative disorders and psychiatric diseases. Adult neurogenesis contains multiple steps including proliferation of neural stem cells, lineage commitments of neural progenitor cells, maturation into functional neurons, and integration into neuronal network. Many intrinsic and extrinsic factors produced from neural stem/progenitor cells and their microenvironment or neurogenic niche take roles in modulating neurogenesis and contribute to the brain repair and functional recoveries in many neurological diseases and psychiatric disorders. In this article, we review current progress about how different growth factors, neurotrophin, neurotransmitters and transcriptional factors work on regulating neurogenic process. In particular, we emphasize the roles of the cellular metabolic factors, such as insulin/IGF signaling, incretins, and lipid metabolic signaling molecules in modulating adult neurogenesis, and discuss their impacts on neurological behaviors. We propose that the metabolic factors could be the new therapeutic targets for adult neurogenesis. Plus, the metabolism-regulating drugs have the potentials for treatment of neurodegenerative diseases and mental disorders.
糖尿病和肥胖等代谢紊乱通常与神经疾病和精神障碍相伴。越来越多的证据表明,细胞代谢因子会影响成体神经发生,并对神经退行性疾病和精神疾病具有调节作用。成体神经发生包含多个步骤,包括神经干细胞的增殖、神经祖细胞的谱系定向、成熟为功能性神经元以及整合到神经网络中。神经干/祖细胞及其微环境或神经发生龛产生的许多内在和外在因素在调节神经发生中发挥作用,并有助于许多神经疾病和精神障碍中的脑修复和功能恢复。在本文中,我们综述了不同生长因子、神经营养因子、神经递质和转录因子如何调节神经发生过程的当前进展。特别地,我们强调细胞代谢因子,如胰岛素/胰岛素样生长因子信号通路、肠促胰岛素和脂质代谢信号分子在调节成体神经发生中的作用,并讨论它们对神经行为的影响。我们提出代谢因子可能是成体神经发生的新治疗靶点。此外,调节代谢的药物具有治疗神经退行性疾病和精神障碍的潜力。