自噬受体激发嵌合体：一种通过自噬降解促进蛋白质聚集体和细胞器去除的新方法

王丽雯; 刘惠美; 李兰芳

doi:10.1631/jzus.B2300853

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自噬受体激发嵌合体：一种通过自噬降解促进蛋白质聚集体和细胞器去除的新方法

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Correspondence | Updated：2024-09-26

自噬受体激发嵌合体：一种通过自噬降解促进蛋白质聚集体和细胞器去除的新方法
Autophagy receptor-inspired chimeras: a novel approach to facilitate the removal of protein aggregates and organelle by autophagy degradation
浙江大学学报（英文版）（B辑：生物医学和生物技术） 2024年页码：1-5
Affiliations：

1.Institute of Pharmaceutical Pharmacology, School of Pharmacy, University of South China, Hengyang 421001, China
2.Hengyang Medical School, University of South China, Hengyang 421001, China
Funds：

the National Natural Science Foundation of China(81970431);the Hunan Provincial Natural Science Foundation of China(2023JJ50136)
DOI：10.1631/jzus.B2300853
中图分类号：
CSTR：
网络出版日期： 2024-09-26 ，

收稿日期： 2023-11-26 ，

修回日期： 2024-03-26 ，
Accepted：

王丽雯,刘惠美,李兰芳.自噬受体激发嵌合体：一种通过自噬降解促进蛋白质聚集体和细胞器去除的新方法[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,

Liwen WANG, Huimei LIU, Lanfang LI. Autophagy receptor-inspired chimeras: a novel approach to facilitate the removal of protein aggregates and organelle by autophagy degradation[J/OL]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2024,1-5.
王丽雯,刘惠美,李兰芳.自噬受体激发嵌合体：一种通过自噬降解促进蛋白质聚集体和细胞器去除的新方法[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）, DOI：10.1631/jzus.B2300853.

Liwen WANG, Huimei LIU, Lanfang LI. Autophagy receptor-inspired chimeras: a novel approach to facilitate the removal of protein aggregates and organelle by autophagy degradation[J/OL]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2024,1-5. DOI： 10.1631/jzus.B2300853.

摘要

神经退行性疾病作为中枢神经系统的遗传性疾病，其主要特征是错误折叠的蛋白质聚集体在大脑神经元中缓慢积累。虽然自噬在降解蛋白质聚集体中发挥着至关重要的作用，但目前尚无有效且广泛适用的方法来降解哺乳动物细胞中的蛋白质聚集体。最新研究表明，合成的自噬受体启发的靶向嵌合体（AceTAC）作为降解剂可将选择性自噬受体-p62的LC3相互作用区（LIR）结构域与抗体结合，AceTAC降解剂可选择性靶向分解不同的蛋白质聚集体（例如mHTT、TDP-43和Tau）。此外，这些降解剂可靶向包括线粒体、过氧化物酶体和内质网在内的细胞器。综上，基于自噬的靶向降解剂AceTAC可作为一种有效治疗神经退行性疾病的新方法。

Abstract

关键词

合成自噬受体自噬p62蛋白质聚集：细胞器

Keywords

references

Barmada SJ, Serio A, Arjun A, et al., 2014. Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models. Nat Chem Biol, 10(8):677-685. https://doi.org/10.1038/nchembio.1563https://doi.org/10.1038/nchembio.1563

Bourdenx M, Martín-Segura A, Scrivo A, et al., 2021. Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome. Cell, 184(10):2696-2714.e25. https://doi.org/10.1016/j.cell.2021.03.048https://doi.org/10.1016/j.cell.2021.03.048

Busche MA, Hyman BT, 2020. Synergy between amyloid-β and tau in Alzheimer’s disease. Nat Neurosci, 23(10):1183-1193. https://doi.org/10.1038/s41593-020-0687-6https://doi.org/10.1038/s41593-020-0687-6

Dragovich PS, 2022. Degrader-antibody conjugates. Chem Soc Rev, 51(10):3886-3897. https://doi.org/10.1039/d2cs00141ahttps://doi.org/10.1039/d2cs00141a

Ji CH, Kim HY, Lee MJ, et al., 2022. The AUTOTAC chemical biology platform for targeted protein degradation via the autophagy-lysosome system. Nat Commun, 13:904. https://doi.org/10.1038/s41467-022-28520-4https://doi.org/10.1038/s41467-022-28520-4

Jiang ZW, Kuo YH, Arkin MR, 2023. Autophagy receptor-inspired antibody-fusion proteins for targeted intracellular degradation. J Am Chem Soc, 145(44):23939-23947. https://doi.org/10.1021/jacs.3c05199https://doi.org/10.1021/jacs.3c05199

Kim G, Gautier O, Tassoni-Tsuchida E, et al., 2020. ALS genetics: gains, losses, and implications for future therapies. Neuron, 108(5):822-842. https://doi.org/10.1016/j.neuron.2020.08.022https://doi.org/10.1016/j.neuron.2020.08.022

Lee J, Sung KW, Bae EJ, et al., 2023. Targeted degradation of α-synuclein aggregates in Parkinson’s disease using the AUTOTAC technology. Mol Neurodegener, 18:41. https://doi.org/10.1186/s13024-023-00630-7https://doi.org/10.1186/s13024-023-00630-7

Li FF, Zhang MZ, Zhang CW, et al., 2020. Nuclear autophagy degrades a geminivirus nuclear protein to restrict viral infection in solanaceous plants. New Phytol, 225(4):1746-1761. https://doi.org/10.1111/nph.16268https://doi.org/10.1111/nph.16268

Li ZY, Wang C, Wang ZY, et al., 2019. Allele-selective lowering of mutant HTT protein by HTT-LC3 linker compounds. Nature, 575(7781):203-209. https://doi.org/10.1038/s41586-019-1722-1https://doi.org/10.1038/s41586-019-1722-1

Li ZY, Zhu CG, Ding Y, et al., 2020. ATTEC: a potential new approach to target proteinopathies. Autophagy, 16(1):185-187. https://doi.org/10.1080/15548627.2019.1688556https://doi.org/10.1080/15548627.2019.1688556

Lin XL, Li S, Zhao Y, et al., 2013. Interaction domains of p62: a bridge between p62 and selective autophagy. DNA Cell Biol, 32(5):220-227. https://doi.org/10.1089/dna.2012.1915https://doi.org/10.1089/dna.2012.1915

Liu HM, Li Q, Li LF, 2023. SARS-CoV-2 ORF7a protein blocks virusclearance by regulating autophagy. Acta Biochim Biophys Sin (Shanghai), 55(8):1334-1336. https://doi.org/10.3724/abbs.2023123https://doi.org/10.3724/abbs.2023123

Llamas E, Koyuncu S, Lee HJ, et al., 2023. In planta expression of human polyQ-expanded huntingtin fragment reveals mechanisms to prevent disease-related protein aggregation. Nat Aging, 3(11):1345-1357. https://doi.org/10.1038/s43587-023-00502-1https://doi.org/10.1038/s43587-023-00502-1

Magalhaes J, Tresse E, Ejlerskov P, et al., 2021. PIAS2-mediated blockade of IFN-β signaling: a basis for sporadic Parkinson disease dementia. Mol Psychiatry, 26(10):6083-6099. https://doi.org/10.1038/s41380-021-01207-whttps://doi.org/10.1038/s41380-021-01207-w

Takahashi D, Moriyama J, Nakamura T, et al., 2019. AUTACs: cargo-specific degraders using selective autophagy. Mol Cell, 76(5):797-810.e10. https://doi.org/10.1016/j.molcel.2019.09.009https://doi.org/10.1016/j.molcel.2019.09.009

Tan X, Cai K, Li JJ, et al., 2023. Coronavirus subverts ER-phagy by hijacking FAM134B and ATL3 into p62 condensates to facilitate viral replication. Cell Rep, 42(4):112286. https://doi.org/10.1016/j.celrep.2023.112286https://doi.org/10.1016/j.celrep.2023.112286

Yang JS, Chen XL, Xu HL, 2021. SQSTM1/p62 droplet-mediated autophagosome formation: insights into Huntington disease. Autophagy, 17(10):3256-3259. https://doi.org/10.1080/15548627.2021.1953820https://doi.org/10.1080/15548627.2021.1953820

Zhang ZG, Yang XF, Song YQ, et al., 2021. Autophagy in Alzheimer’s disease pathogenesis: therapeutic potential and future perspectives. Ageing Res Rev, 72:101464. https://doi.org/10.1016/j.arr.2021.101464https://doi.org/10.1016/j.arr.2021.101464

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