美国加州大学伯克利分校Andrew Dillin小组取得一项新进展。他们的研究发现，在秀丽隐杆线虫中，四个胶质细胞通过神经肽信号来调节内质网的抗逆性和寿命。这一研究成果于2020年1月24日发表在国际顶尖学术期刊《科学》上。

研究人员在星形胶质样胶质细胞亚群中表达了组成型活跃的内质网未折叠蛋白反应（UPRER）转录因子XBP-1s，从而延长了秀丽隐杆线虫的寿命。胶质细胞的XBP-1s启动了远端细胞中UPRER的强大细胞非自主型激活，并使动物对蛋白质聚集和慢性ER应激更具抵抗力。缺乏神经肽加工和分泌的突变体抑制了UPRER的胶质细胞非自主诱导和寿命延长。因此，星形胶质样神经胶质细胞在调节机体内质网应激抵抗和长寿中发挥了作用。

据了解，神经系统感知细胞应激并协调蛋白质稳态的能力对于机体的健康至关重要。不幸的是，随着年龄的增长，缓解蛋白稳态紊乱的应激反应（例如UPRER）会变得无效。

附：英文原文

Title: Four glial cells regulate ER stress resistance and longevity via neuropeptide signaling in C. elegans

Author: Ashley E. Frakes, Melissa G. Metcalf, Sarah U. Tronnes, Raz Bar-Ziv, Jenni Durieux, Holly K. Gildea, Nazineen Kandahari, Samira Monshietehadi, Andrew Dillin

Issue&Volume: 2020/01/24

Abstract: The ability of the nervous system to sense cellular stress and coordinate protein homeostasis is essential for organismal health. Unfortunately, stress responses that mitigate disturbances in proteostasis, such as the unfolded protein response of the endoplasmic reticulum (UPRER), become defunct with age. In this work, we expressed the constitutively active UPRER transcription factor, XBP-1s, in a subset of astrocyte-like glia, which extended the life span in Caenorhabditis elegans. Glial XBP-1s initiated a robust cell nonautonomous activation of the UPRER in distal cells and rendered animals more resistant to protein aggregation and chronic ER stress. Mutants deficient in neuropeptide processing and secretion suppressed glial cell nonautonomous induction of the UPRER and life-span extension. Thus, astrocyte-like glial cells play a role in regulating organismal ER stress resistance and longevity.

DOI: 10.1126/science.aaz6896

Source: https://science.sciencemag.org/content/367/6476/436