伦敦帝国学院Simone Di Giovanni小组宣布他们的研究开发出了通过戊糖磷酸途径的糖酵解分流是神经系统感觉稳态和轴突再生的代谢检查点。2026年1月5日出版的《细胞》杂志发表了这项成果。
该课题组发现了戊糖磷酸通路（PPP）在外周感觉轴突中的一个意想不到的作用，它支持损伤后的稳态机械感觉和轴突再生。该研究组发现，PPP在坐骨神经轴突中丰富且活跃，它通过产生NADPH来维持氧化还原平衡，从而实现生理机械感觉。
然而，坐骨神经损伤后，再生需要PPP通过核糖-5-磷酸促进核糖核苷酸合成。相反，该通路在脊髓损伤（SCI）后保持失活，导致再生衰竭。通过神经元转酮醇酶过表达或口服补充核糖，PPP的再激活可促进代谢重编程，恢复感觉和运动轴突生长，并改善脊髓损伤后神经系统的恢复。这些发现表明PPP是感觉神经元生理和再生的代谢检查点，突出了其在中枢神经系统修复方面的治疗潜力。
据悉，神经系统的内稳态和修复被认为依赖于不同的分子程序。
附：英文原文
Title: A glycolytic shunt via the pentose phosphate pathway is a metabolic checkpoint for nervous system sensory homeostasis and axonal regeneration
Author: Yayue Song, Lucia Luengo-Gutierrez, Virag Sagi-Kiss, Guiping Kong, Helen Huang, Moritz Steinruecke, Luming Zhou, Zhulin Yuan, Francesco De Virgiliis, Istvan Pap, Charlotte Decourt, Yuyang Yan, Hee Hwan Park, Hanqi Zhang, Jiahui Wei, Elizabeth Want, Xuemei Tong, Zoltan Takats, Simone Di Giovanni
Issue&Volume: 2026-01-05
Abstract: Homeostasis and repair in the nervous system are thought to rely on distinct molecular programs. Here, we uncover an unexpected role for the pentose phosphate pathway (PPP) in peripheral sensory axons, where it supports both homeostatic mechanosensation and axonal regeneration after injury. We show that the PPP is enriched and active in sciatic nerve axoplasms, where it maintains redox balance via NADPH production, enabling physiological mechanical sensation. However, following sciatic nerve injury, the PPP is required for regeneration by fueling ribonucleotide synthesis through ribose-5-phosphate. In contrast, this pathway remains inactive after spinal cord injury (SCI), contributing to regenerative failure. Reactivation of the PPP, through neuronal transketolase overexpression or oral ribose supplementation, promotes metabolic reprogramming, restores sensory and motor axonal growth, and improves neurological recovery after SCI. These findings propose the PPP as a metabolic checkpoint in sensory neuron physiology and regeneration, highlighting its therapeutic potential for central nervous system repair.
DOI: 10.1016/j.cell.2025.12.003
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01379-0