A novel small-molecule PROTAC selectively promotes tau clearance to improve cognitive functions in Alzheimer-like models
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, which provides a promising drug candidate for AD and the related tauopathies.
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Induced turnover of tau by the UPS, and the degradability of tau species, has been demonstrated by a tau-KEAP1 chimeric peptide PROTAC molecule, as well as by a VHL-tau PROTAC.
“Importantly, induced turnover of tau by the UPS, and the degradability of tau species, has been demonstrated by a tau–kelch-like ECH-associated protein 1 (KEAP1) chimeric peptide PROTAC molecule188, as well as by a VHL–tau PROTAC189.”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [189]
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- Authors
- Wang, W., Zhou, Q., Jiang, T., Li, S., Ye, J., Zheng, J., Wang, X., Liu, Y., Deng, M., Ke, D., Wang, Q., Wang, Y., & Wang, J.-Z.
- Affiliations
- Huazhong University of Science and Technology (CN)
- Nantong University (CN)
- Corresponding author
- Wang, Yipeng
- Wang, Jian-Zhi
- Venue
- Theranostics
- Publisher
- Ivyspring International Publisher
- Published
- 2021
- Volume
- 11
- Issue
- 11
- Pages
- 5279-5295
- ISSN
- 1838-7640 (ISSN-L)
- PMC
- PMC8039949
- OpenAlex
- W3139364923
- Cited by
- 242
- References
- 41
- Citations by year
- 2026: 53 · 2025: 62 · 2024: 51 · 2023: 32 · 2022: 33 · 2021: 11
- FWCI
- 20.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Theranostics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- PROTACs, small-molecule degraders, tau clearance, Alzheimer's disease, tauopathy, cognitive function, drug candidates
- MeSH terms
- Alzheimer Disease, Animals, Brain, Cell Line, Cognition, Disease Models, Animal, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Neuronal Plasticity, Neurons, tau Proteins, Tauopathies, Proteasome Endopeptidase Complex, Mice, Small Molecule Libraries, Ubiquitination, HEK293 Cells, Proteolysis
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