Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, Hunan, China.
Department of Pharmacy, The First Affiliated Hospital, University of South China, Hengyang, China.
Free Radic Biol Med. 2021 Feb 1;163:125-134. doi: 10.1016/j.freeradbiomed.2020.12.013. Epub 2020 Dec 21.
Mitochondrial unfolded protein response (UPR) is a mitochondria stress response, which the transcriptional activation programs of mitochondrial chaperone proteins and proteases are initiated to maintain proteostasis in mitochondria. Additionally, the activation of UPR delays aging and extends lifespan by maintaining mitochondrial proteostasis. Growing evidences suggests that UPR plays an important role in diverse human diseases, especially ageing-related diseases. Therefore, this review focuses on the role of UPR in ageing and ageing-related neurodegenerative diseases such as Alzheimer's disease, Huntington's disease and Parkinson's disease. The activation of UPR and the high expression of UPR components contribute to longevity extension. The activation of UPR may ameliorate Alzheimer's disease, Parkinson's disease and Huntington's disease. Besides, UPR is also involved in the occurrence and development of cancers and heart diseases. UPR contributes to the growth, invasive and metastasis of cancers. UPR has paradoxical roles in heart diseases. UPR not only protects against heart damage, but may sometimes aggravates the development of heart diseases. Considering the pleiotropic actions of UPR system, targeting UPR pathway may be a potent therapeutic avenue for neurodegenerative diseases, cancers and heart diseases.
线粒体未折叠蛋白反应（UPR）是一种线粒体应激反应，其中线粒体伴侣蛋白和蛋白酶的转录激活程序被启动，以维持线粒体中的蛋白质稳态。此外，UPR 的激活通过维持线粒体蛋白质稳态来延缓衰老并延长寿命。越来越多的证据表明，UPR 在多种人类疾病中发挥重要作用，尤其是与衰老相关的疾病。因此，本综述重点讨论了 UPR 在衰老和与衰老相关的神经退行性疾病（如阿尔茨海默病、亨廷顿病和帕金森病）中的作用。UPR 的激活和 UPR 成分的高表达有助于延长寿命。UPR 的激活可能改善阿尔茨海默病、帕金森病和亨廷顿病。此外，UPR 还参与癌症和心脏病的发生和发展。UPR 有助于癌症的生长、侵袭和转移。UPR 在心脏病中具有矛盾的作用。UPR 不仅可以防止心脏损伤，但有时可能会加重心脏病的发展。考虑到 UPR 系统的多效性作用，靶向 UPR 途径可能是神经退行性疾病、癌症和心脏病的有效治疗途径。
