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Correction to:Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model

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Protein & Cell 2022年第3期13卷 227-229页

作者： Xiaoyan Xu Yaqin Sun Xufeng Cen Bing Shan Qingwei Zhao Tingxue Xie Zhe Wang Tingjun Hou Yu Xue Mengmeng Zhang Di Peng Qiming Sun Cong Yi Ayaz Najafov Hongguang Xia Department of Biochemistry&Research Center of Clinical Pharmacy of The First Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China Liangzhu Laboratory Zhejiang University Medical CenterHangzhou 311121China Department of Cell Biology Harvard Medical SchoolBostonMA 02115USA Interdisciplinary Research Center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 201203China College of Pharmaceutical Sciences Hangzhou Institute of innovative MedicineZhejiang UniversityHangzhou 310058China Key Laboratory of Molecular Biophysics of Ministry of Education Hubei Bioinformatics and Molecular Imaging Key LaboratoryCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China

CORRECTION TO:PROTEIN CELL HTTPS://***/10.1007/S13238-021-00858-3 In legend of figure 1,this sentence“(C)293THK cells were treated as in a”should be corrected as“(C)293THK cells were treated as in(A)”.In legend of figure 2,“E-64D(10μmol/L)”in description of panel(B)should be removed.In section“Metformin activates chaperone-mediated autophagy”of RESULTS,E-64D in sentence“Metformininduced degradation of HK2 and PKM2 was blocked by lysosomal inhibitors(E-64D,Bafilomycin A1 and Leupeptin+NH4Cl)”should be removed.

关键词： Metformin Alzheimer removed

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Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model

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Protein & Cell 2021年第10期12卷 769-787页

Chaperone-mediated autophagy(CMA)is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases.However,the mechanisms that regulate CMA are not fully understood.Here,using unbiased drug screening approaches,we discover Metformin,a drug that is commonly the first medication prescribed for type 2 diabetes,can induce CMA.We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA,Hsc70,and its activation.Notably,we find that amyloid-beta precursor protein(APP)is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent manner.The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity.Importantly,we find that in the APP/PS1 mouse model of Alzheimer's disease(AD),activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβplaque levels and reverses the molecular and behavioral AD phenotypes.Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases,such as AD,where such therapeutic intervention could be beneficial.

关键词： chaperone-mediated autophagy Metformin TAK1 IKKα/β Hsc70 APP Alzheimer’s disease

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