小柯机器人

南京中医药大学胡刚团队发现，有氧糖酵解是神经元胞体葡萄糖代谢的主要方式并可防止氧化损伤。这一研究成果于2023年11月23日在线发表在《自然—神经科学》期刊上。

研究人员证明了在基础和激活状态下，神经元胞体比末梢进行更高水平的有氧糖酵解和更低水平的氧化磷酸化（OXPHOS）。研究人员发现，糖酵解酶丙酮酸激酶 2（PKM2）主要定位于胞体而非末梢。在小鼠体内缺失Pkm2会导致神经元体部从有氧糖酵解转变为OXPHOS，从而导致氧化损伤和多巴胺能神经元的逐渐丧失。这些发现更新了神经元在基础条件下一致使用OXPHOS的传统观点，并强调了胞体有氧糖酵解在维持抗氧化能力方面的重要作用。

研究人员表示，一般认为，在基础条件下，神经元主要通过线粒体OXPHOS产生ATP，只有当神经元被激活并需要满足更高的能量需求时，糖酵解活动才会占主导地位。然而，神经元胞体和轴突末端之间的葡萄糖代谢是否存在差异仍是未知数。

附：英文原文

Title: Aerobic glycolysis is the predominant means of glucose metabolism in neuronal somata, which protects against oxidative damage

Author: Wei, Yao, Miao, QianQian, Zhang, Qian, Mao, Shiyu, Li, Mengke, Xu, Xing, Xia, Xian, Wei, Ke, Fan, Yu, Zheng, Xinlei, Fang, Yinquan, Mei, Meng, Zhang, Qingyu, Ding, Jianhua, Fan, Yi, Lu, Ming, Hu, Gang

Issue&Volume: 2023-11-23

Abstract: It is generally thought that under basal conditions, neurons produce ATP mainly through mitochondrial oxidative phosphorylation (OXPHOS), and glycolytic activity only predominates when neurons are activated and need to meet higher energy demands. However, it remains unknown whether there are differences in glucose metabolism between neuronal somata and axon terminals. Here, we demonstrated that neuronal somata perform higher levels of aerobic glycolysis and lower levels of OXPHOS than terminals, both during basal and activated states. We found that the glycolytic enzyme pyruvate kinase 2 (PKM2) is localized predominantly in the somata rather than in the terminals. Deletion of Pkm2 in mice results in a switch from aerobic glycolysis to OXPHOS in neuronal somata, leading to oxidative damage and progressive loss of dopaminergic neurons. Our findings update the conventional view that neurons uniformly use OXPHOS under basal conditions and highlight the important role of somatic aerobic glycolysis in maintaining antioxidant capacity.

DOI: 10.1038/s41593-023-01476-4

Source: https://www.nature.com/articles/s41593-023-01476-4

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex