杜克大学闫冬课题组的一项最新研究揭示了热休克蛋白作为信号分子介导秀丽隐杆线虫衰老过程中神经元-胶质细胞间的通讯。2025年6月18日出版的《自然—神经科学》杂志发表了这项成果。

在这里，研究团队展示了神经元-胶质细胞信号转导的新机制，其中神经元通过细胞外囊泡将蛋白质传递给胶质细胞，激活胶质信号通路。课题组研究人员发现在秀丽隐杆线虫（Caenorhabditis elegans）的两栖感觉器官中，不同的感觉神经元表现出不同的衰老速度。这种衰老的差异是由神经元和神经胶质之间的相互作用所控制的。该研究组证明了早期衰老的神经元可以通过细胞外囊泡将热休克蛋白传递给胶质细胞。这些神经元热休克蛋白激活神经胶质IRE1-XBP1通路，导致软骨素合成酶的转录调节，以保护嵌入神经胶质的神经元免受衰老相关功能下降的影响。因此，他们的研究揭示了神经系统中神经元-胶质细胞交流的新机制，并为他们对大脑衰老的理解提供了新的见解。

据了解，神经系统主要由神经元和神经胶质组成，它们之间的交流在调节大脑的发育和功能方面具有深远的作用。神经元-胶质细胞信号转导是通过细胞膜上的配体-受体相互作用分泌信号介导的。

附：英文原文

Title: Heat shock proteins function as signaling molecules to mediate neuron–glia communication in C. elegans during aging

Author: Wu, Jieyu, Yarmey, Victoria R., Yang, Olivia Jiaming, Soderblom, Erik J., San-Miguel, Adriana, Yan, Dong

Issue&Volume: 2025-06-18

Abstract: The nervous system is primarily composed of neurons and glia, and the communication between them has profound roles in regulating the development and function of the brain. Neuron–glia signal transduction is known to be mediated by secreted signals through ligand–receptor interactions on the cell membrane. Here we show a new mechanism for neuron–glia signal transduction, wherein neurons transmit proteins to glia through extracellular vesicles, activating glial signaling pathways. We find that in the amphid sensory organ of Caenorhabditis elegans, different sensory neurons exhibit varying aging rates. This discrepancy in aging is governed by the cross-talk between neurons and glia. We demonstrate that early aged neurons can transmit heat shock proteins to glia via extracellular vesicles. These neuronal heat shock proteins activate the glial IRE1–XBP1 pathway, leading to the transcriptional regulation of chondroitin synthases to protect glia-embedded neurons from aging-associated functional decline. Therefore, our studies unveil a new mechanism for neuron–glia communication in the nervous system and provide new insights into our understanding of brain aging.

DOI: 10.1038/s41593-025-01989-0

Source: https://www.nature.com/articles/s41593-025-01989-0