Department of Orthodontics, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, Zhejiang, China.
Department of Implantology, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, Zhejiang, China.
Cell Mol Biol Lett. 2022 Jan 3;27(1):2. doi: 10.1186/s11658-021-00302-8.
Sestrins (Sesns), highly conserved stress-inducible metabolic proteins, are known to protect organisms against various noxious stimuli including DNA damage, oxidative stress, starvation, endoplasmic reticulum (ER) stress, and hypoxia. Sesns regulate metabolism mainly through activation of the key energy sensor AMP-dependent protein kinase (AMPK) and inhibition of mammalian target of rapamycin complex 1 (mTORC1). Sesns also play pivotal roles in autophagy activation and apoptosis inhibition in normal cells, while conversely promoting apoptosis in cancer cells. The functions of Sesns in diseases such as metabolic disorders, neurodegenerative diseases, cardiovascular diseases, and cancer have been broadly investigated in the past decades. However, there is a limited number of reviews that have summarized the functions of Sesns in the pathophysiological processes of human diseases, especially musculoskeletal system diseases. One aim of this review is to discuss the biological functions of Sesns in the pathophysiological process and phenotype of diseases. More significantly, we include some new evidence about the musculoskeletal system. Another purpose is to explore whether Sesns could be potential biomarkers or targets in the future diagnostic and therapeutic process.
Sestrins（Sesns）是高度保守的应激诱导代谢蛋白，已知可保护生物体免受各种有害刺激，包括 DNA 损伤、氧化应激、饥饿、内质网（ER）应激和缺氧。Sesns 主要通过激活关键能量传感器 AMP 依赖的蛋白激酶（AMPK）和抑制哺乳动物雷帕霉素靶蛋白复合物 1（mTORC1）来调节代谢。Sesns 在正常细胞中还在自噬激活和凋亡抑制中发挥关键作用，而在癌细胞中则促进凋亡。在过去的几十年中，Sesns 在代谢紊乱、神经退行性疾病、心血管疾病和癌症等疾病中的作用已经得到了广泛的研究。然而，仅有少量综述总结了 Sesns 在人类疾病病理生理过程中的作用，特别是在肌肉骨骼系统疾病中的作用。本文的目的之一是讨论 Sesns 在疾病的病理生理过程和表型中的生物学功能。更重要的是，我们还包括了一些关于肌肉骨骼系统的新证据。另一个目的是探讨 Sesns 是否可以成为未来诊断和治疗过程中的潜在生物标志物或靶点。
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