Endoplasmic reticulum (ER) is a subcellular organelle involved in protein folding and processing. ER stress constitutes a cellular process characterized by accumulation of misfolded proteins, impaired lipid metabolism and induction of inflammatory responses. ER stress has been suggested to be involved in several human pathologies, including neurodegenerative diseases and obesity. Different studies have shown that both neurodegenerative diseases and obesity trigger similar cellular responses to ER stress. Moreover, both diseases are assessed in astrocytes as evidences suggest these cells as key regulators of brain homeostasis. However, the exact contributions to the effects of ER stress in astrocytes in the various neurodegenerative diseases and its relation with obesity are not well known. Here, we discuss recent advances in the understanding of molecular mechanisms that regulate ER stress-related disorders in astrocytes such as obesity and neurodegeneration. Moreover, we outline the correlation between the activated proteins of the unfolded protein response (UPR) in these pathological conditions in order to identify possible therapeutic targets for ER stress in astrocytes. We show that ER stress in astrocytes shares UPR activation pathways during both obesity and neurodegenerative diseases, demonstrating that UPR related proteins like ER chaperone GRP 78/Bip, PERK pathway and other exogenous molecules ameliorate UPR response and promote neuroprotection.

内质网（ER）是参与蛋白质折叠和加工的亚细胞器。内质网应激构成一个细胞过程，其特征是蛋白质折叠错误，脂质代谢受损和炎症反应的诱导。内质网应激被认为与多种人类病理有关，包括神经退行性疾病和肥胖。不同的研究表明，神经退行性疾病和肥胖都触发类似的细胞对内质网应激的反应。而且，两种疾病都在星形胶质细胞中评估，因为有证据表明这些细胞是脑稳态的关键调节因子。然而，在各种神经退行性疾病中，星形胶质细胞对内质网应激的影响的确切贡献及其与肥胖的关系尚不清楚。这里，我们讨论了解调节星形胶质细胞内质网应激相关疾病（例如肥胖症和神经退行性疾病）的分子机制的最新进展。此外，我们概述了在这些病理条件下未折叠蛋白应答（UPR）的活化蛋白之间的相关性，以鉴定星形胶质细胞内ER应激的可能治疗靶点。我们显示，在肥胖症和神经退行性疾病期间，星形胶质细胞中的ER应力共享UPR激活途径，表明ER分子伴侣GRP 78 / Bip，PERK途径和其他外源性分子等UPR相关蛋白改善了UPR反应并促进了神经保护作用。我们概述了在这些病理条件下未折叠蛋白应答（UPR）的活化蛋白之间的相关性，以鉴定星形胶质细胞内质网应激的可能治疗靶标。我们显示，在肥胖症和神经退行性疾病期间，星形胶质细胞中的ER应力共享UPR激活途径，表明ER伴侣GRP 78 / Bip，PERK途径和其他外源性分子等UPR相关蛋白改善了UPR反应并促进了神经保护作用。我们概述了在这些病理条件下未折叠蛋白应答（UPR）的活化蛋白之间的相关性，以鉴定星形胶质细胞内质网应激的可能治疗靶标。我们显示，在肥胖症和神经退行性疾病期间，星形胶质细胞中的ER应力共享UPR激活途径，表明ER伴侣GRP 78 / Bip，PERK途径和其他外源性分子等UPR相关蛋白改善了UPR反应并促进了神经保护作用。