Zhang Shuyuan, Zhao Juan, Quan Zhenzhen, Li Hui, Qing Hong
Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China.
Aerospace Medical Center, Aerospace Center Hospital, Beijing, China.
Front Neurosci. 2022 Apr 5;16:853911. doi: 10.3389/fnins.2022.853911. eCollection 2022.
The contribution of organelles to neural development has received increasing attention. Studies have shown that organelles such as mitochondria, endoplasmic reticulum (ER), lysosomes, and endosomes play important roles in neurogenesis. Specifically, metabolic switching, reactive oxygen species production, mitochondrial dynamics, mitophagy, mitochondria-mediated apoptosis, and the interaction between mitochondria and the ER all have roles in neurogenesis. Lysosomes and endosomes can regulate neurite growth and extension. Moreover, metabolic reprogramming represents a novel strategy for generating functional neurons. Accordingly, the exploration and application of mechanisms underlying metabolic reprogramming will be beneficial for neural conversion and regenerative medicine. There is adequate evidence implicating the dysfunction of cellular organelles-especially mitochondria-in neurodegenerative disorders, and that improvement of mitochondrial function may reverse the progression of these diseases through the reinforcement of adult neurogenesis. Therefore, these organelles have potential as therapeutic targets for the treatment of neurodegenerative diseases. In this review, we discuss the function of these organelles, especially mitochondria, in neural development, focusing on their potential as therapeutic targets in neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis.
细胞器对神经发育的贡献已受到越来越多的关注。研究表明,线粒体、内质网(ER)、溶酶体和内体等细胞器在神经发生中发挥着重要作用。具体而言,代谢转换、活性氧生成、线粒体动力学、线粒体自噬、线粒体介导的细胞凋亡以及线粒体与内质网之间的相互作用在神经发生中均发挥作用。溶酶体和内体可调节神经突的生长和延伸。此外,代谢重编程是生成功能性神经元的一种新策略。因此,探索和应用代谢重编程的潜在机制将有利于神经转化和再生医学。有充分证据表明细胞器功能障碍——尤其是线粒体功能障碍——与神经退行性疾病有关,并且改善线粒体功能可能通过增强成体神经发生来逆转这些疾病的进展。因此,这些细胞器具有作为神经退行性疾病治疗靶点的潜力。在本综述中,我们讨论这些细胞器,尤其是线粒体,在神经发育中的功能,重点关注它们作为神经退行性疾病(包括阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症)治疗靶点的潜力。