Efficient amyloid-β degradation in Alzheimer’s disease using SPYTACs

Teng, Fei; Liu, Jing; Cui, Tongtong; Tan, Xiangtian; Liu, Kailun; Hou, Zongren; (54356), Li Zhou; Xie, Yuanzhi; Li, Rongqi; Li, Da; Li, Bojin; Wang, Dongmei; Zhou, Qi; Hu, B. P.; Li, Wei

doi:10.1016/j.cell.2026.01.034

articleCellMar 4, 2026HYBRID OA

Efficient amyloid-β degradation in Alzheimer’s disease using SPYTACs

FTFei Teng JLJing Liu TCTongtong Cui XTXiangtian Tan KLKailun Liu

University of Chinese Academy of Sciences · Institute of Zoology · +1 more institution

PubMed

Indexed incrossrefpubmed

Abstract

Clearance of aberrant cerebral amyloid-β (Aβ) deposits represents a promising therapeutic strategy for Alzheimer's disease (AD), yet current anti-Aβ immunotherapy raises safety concerns due to frequent adverse effects. Extracellular targeted protein degradation (eTPD) offers an approach for safe and efficient clearance of disease-causing proteins. Here, we develop a next-generation eTPD platform, synthetic peptide-programmed lysosome-targeting chimeras (SPYTACs), using entirely synthesized bispecific peptides. Leveraging low-density lipoprotein receptor-related protein 1 (LRP1), SPYTACs effectively facilitate targeted degradation of extracellular proteins and enable transcytosis across the blood-brain barrier.…

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Topics & keywords

Topics

Keywords

Degradation (telecommunications)
Disease
Mutation

UN Sustainable Development Goals

Zero hunger

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