Related Experiment Video
Updated: Jun 13, 2025
09:22
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
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Co-opting templated aggregation to degrade pathogenic tau assemblies and improve motor function.
Lauren V C Miller1, Guido Papa2, Marina Vaysburd2
1UK Dementia Research Institute at the University of Cambridge, Department of Clinical Neurosciences, Hills Road, Cambridge CB2 0AH, UK; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Cell
|September 14, 2024
Summary
A novel "RING-Bait" strategy targets toxic protein aggregates in neurodegenerative diseases. This approach selectively degrades pathological tau aggregates while sparing functional proteins, offering a promising therapeutic avenue.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Protein aggregation is a hallmark of neurodegenerative diseases, posing a significant therapeutic challenge.
- Current strategies struggle to selectively remove aggregates without affecting functional proteins.
Purpose of the Study:
- To develop a novel therapeutic strategy, "RING-Bait," for selective degradation of protein aggregates.
- To demonstrate the efficacy of RING-Bait in targeting and removing pathological tau aggregates.
Main Methods:
- Engineered a "RING-Bait" construct combining an aggregating protein sequence with an E3 ubiquitin ligase.
- Utilized adeno-associated virus (AAV) for brain-penetrant delivery in a P301S tau transgenic mouse model.
- Assessed aggregate degradation, pathology reduction, and functional improvement.
Main Results:
- RING-Bait specifically degraded tau aggregates while sparing soluble tau.
- The strategy was effective against seeded and cell-autonomous tau aggregation, including from Alzheimer's disease and progressive supranuclear palsy brain extracts.
- In vivo treatment reduced tau pathology and improved motor function in P301S tau mice.
Conclusions:
- RING-Bait represents a novel and effective strategy for selectively clearing protein aggregates in neurodegenerative diseases.
- This approach shows potential for treating tauopathies and can be adapted for other proteinopathies.
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