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| 1 | Autophagy and beyond:Unraveling the complexity of UNC-51-like kinase 1(ULK1)from biological functions to therapeutic implications显示文摘UNC-51-like kinase 1(ULK1),as a serine/threonine kinase,is an autophagic initiator in mammals and a homologous protein of autophagy related protein(Atg)1 in yeast and of UNC-51 in Caenorhabditis elegans.ULK1 is well-known for autophagy activation,which is evolutionarily conserved in protein transport and indispensable to maintain cell homeostasis.As the direct target of energy and nutrition-sensing kinase,ULK1 may contribute to the distribution and utilization of cellular resources in response to metabolism and is closely associated with multiple pathophysiological processes.Moreover,ULK1 has been widely reported to play a crucial role in human diseases,including cancer,neurodegenerative diseases,cardiovascular disease,and infections,and subsequently targeted small-molecule inhibitors or activators are also demonstrated.Interestingly,the non-autophagy function of ULK1 has been emerging,indicating that non-autophagy-relevant ULK1 signaling network is also linked with diseases under some specific contexts.Therefore,in this review,we summarized the structure and functions of ULK1 as an autophagic initiator,with a focus on some new approaches,and further elucidated the key roles of ULK1 in autophagy and non-autophagy.Additionally,we also discussed the relationships between ULK1 and human diseases,as well as illustrated a rapid progress for better understanding of the discovery of more candidate small-molecule drugs targeting ULK1,which will provide a clue on novel ULK1-targeted therapeutics in the future. | Ling Zou Minru Liao Yongqi Zhen Shiou Zhu Xiya Chen Jin Zhang Yue Hao Bo Liu | 2022 | Acta Pharmaceutica Sinica B2022，12，10： | 3 |
| 2 | Rab蛋白在阿尔茨海默病发病机制中作用的研究进展显示文摘阿尔茨海默病(Alzheimer's disease, AD)最显著的两大病理改变为细胞外β淀粉样蛋白(β-amyloid, Aβ)沉积形成的老年斑和神经元内tau蛋白过度磷酸化形成的神经纤维缠结。近来有越来越多的研究显示,多种小GTP酶Ras相关蛋白(Ras-related protein, Rab)与AD发病密切相关。作为细胞内膜类结构转运、加工的关键调节因素,Rab家族蛋白的改变是引发AD中囊泡转运异常的主要因素之一,同时也参与了AD中Aβ、tau等病理改变的发生和发展。本文就Rab蛋白的主要功能及其在AD发病机制中的作用进行了系统综述。 | 张菁 江海天 韩道滨 于卉 王路雯 苏擘 | 2023 | 生理学报2023，75，6： | 1 |
| 3 | Isoform-and cell-state-specific APOE homeostasis and function显示文摘Apolipoprotein E is the major lipid transporter in the brain and an important player in neuron-astrocyte metabolic coupling.It ensures the survival of neurons under stressful conditions and hyperactivity by nourishing and detoxifying them.Apolipoprotein E polymorphism,combined with environmental stresses and/or age-related alterations,influences the risk of developing late-onset Alzheimer’s disease.In this review,we discuss our current knowledge of how apolipoprotein E homeostasis,i.e.its synthesis,secretion,degradation,and lipidation,is affected in Alzheimer’s disease. | Karina Lindner Anne-Claude Gavin | 2024 | Neural Regeneration Research2024，19，11： | 0 |
| 4 | Impaired autophagy in amyloid-beta pathology:A traditional review of recent Alzheimer's research显示文摘Alzheimer’s disease(AD) is the most prevalent neurodegenerative disorder. The major pathological changes in AD progression are the generation and accumulation of amyloid-beta(Aβ) peptides as well as the presence of abnormally hyperphosphorylated tau proteins in the brain. Autophagy is a conserved degradation pathway that eliminates abnormal protein aggregates and damaged organelles. Previous studies have suggested that autophagy plays a key role in the production and clearance of Aβ peptides to maintain a steady-state of Aβ peptides levels.However, a growing body of evidence suggests that autophagy is significantly impaired in the pathogenesis of AD, especially in Aβ metabolism. Therefore, this article reviews the latest studies concerning the mechanisms of autophagy, the metabolism of Aβ peptides, and the defective autophagy in the production and clearance of Aβpeptides. Here, we also summarize the established and new strategies for targeting autophagy in vivo and through clinical AD trials to identify gaps in our knowledge and to generate further questions. | Minghao Yuan Yangyang Wang Zhenting Huang Feng Jing Peifeng Qiao Qian Zou Jing Li Zhiyou Cai | 2023 | The Journal of Biomedical Research2023，37，1： | 0 |
| 5 | Targeting autophagy and beyond:Deconvoluting the complexity of Beclin-1 from biological function to cancer therapy显示文摘AbstracBteclin-1 is the firstly-identified mammalian protein of the autophagy machinery,which functions as a molecular scaffold for the assembly of PI3KC3(class II phosphatidylinositol 3 kinase)complex,thus controlling autophagy induction and other cellular trafficking events.Notably,there is mounting evidence establishing the implications of Beclin-1 in diverse tumorigenesis processes,including tumor suppression and progression as well as resistance to cancer therapeutics and CSC(cancer stem-like cell)maintenance.More importantly,Beclin-1 has been confirmed as a potential target for the treatment of multiple cancers.In this review,we provide a comprehensive survey of the structure,functions,and regulations of Beclin-1,and we discuss recent advances in understanding the controversial roles of Beclin-1 in oncology.Moreover,we focus on summarizing the targeted Beclin-1-regulating strategies in cancer therapy,providing novel insights into a promising strategy for regulating Beclin-1 to improvecancer therapeutics in thefuture. | Jing Ye Jin Zhang Yanghui Zhu Lian Wang Xian Jiang Bo Liu Gu He | 2023 | Acta Pharmaceutica Sinica B2023，13，12： | 0 |
| 6 | 以哺乳动物雷帕霉素靶蛋白为靶点治疗阿尔茨海默病的研究进展显示文摘哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)调节细胞存活、增殖和代谢。阿尔茨海默病(Alzheimer's disease,AD)是一种常见的神经系统退行性疾病,发病机理复杂,与衰老密切相关。研究发现,AD的病理发展过程中经常伴随着mTOR活性的变化,但尚不清楚mTOR在AD发病机制中的作用。本文首先介绍了mTOR的复合物及其信号通路,重点综述了mTOR信号通路对突触可塑性和记忆功能、自噬作用、β-淀粉样蛋白(amyloid-β,Aβ)、Tau蛋白和脑胰岛素抵抗等AD病理特征的影响,其次阐述了m TOR两种信号通路在抗衰老和延长寿命方面的调控作用,最后介绍了mTOR抑制剂在AD病理研究中的应用,为延缓和改善AD提供新的思路。 | 王准 孙谕莹 黄汉昌 | 2023 | 中国临床药理学与治疗学2023，28，12： | 0 |
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