JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Autophagy receptor-inspired chimeras: A novel approach to facilitate the removal of protein aggregates and organelle by autophagy degradation

Author(s): Liwen WANG, Huimei LIU, Lanfang LI
Affiliation(s): Institute of Pharmaceutical Pharmacology, School of Pharmacy, University of South China, Hengyang 421001, China; more
Corresponding email(s): 2005001782@usc.edu.cn
Key Words: Synthetic autophagy receptors; Autophagy; p62; Protein aggregates; Organelles

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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]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2300853

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author="Liwen WANG, Huimei LIU, Lanfang LI",
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year="in press",
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doi="https://doi.org/10.1631/jzus.B2300853"
}

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%T Autophagy receptor-inspired chimeras: A novel approach to facilitate the removal of protein aggregates and organelle by autophagy degradation
%A Liwen WANG
%A Huimei LIU
%A Lanfang LI
%J Journal of Zhejiang University SCIENCE B
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%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2300853"

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A1 - Liwen WANG
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A1 - Lanfang LI
J0 - Journal of Zhejiang University Science B
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%@ 1673-1581
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PB - Zhejiang University Press & Springer
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doi="https://doi.org/10.1631/jzus.B2300853"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Neurodegenerative diseases are genetic disorders of the central nervous system. Their key feature is the slow accumulation of misfolded protein deposits in brain neurons. While autophagy is known to play a crucial role in degrading protein aggregates, there is currently no effective and widely applicable method for the degradation of protein aggregates in mammalian cells. The latest data demonstrate that synthetic autophagy receptor-inspired targeting chimeras (AceTACs) act as degraders that can combine the LIR domain of the selective autophagy receptor-p62 with antibodies. Different protein aggregates (such as mHTT, TDP-43, and Tau) can be selectively targeted for disintegration by AceTAC degraders. Moreover, these degraders can target intracellular organelles including mitochondria, peroxisomes, and endoplasmic reticulum. Therefore, AceTACs represent promising autophagy-based targeted degraders that could offer a novel approach to effectively treat neurodegenerative diseases..

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