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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
Modulation and detection of tau aggregation with small-molecule ligands
Edward Chang1, Nicolette S Honson, Bhaswati Bandyopadhyay
1Center for Molecular Neurobiology, Department of Molecular and Cellular Biochemistry, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA.
Current Alzheimer Research
|October 31, 2009
Summary
Small molecules interact with tau protein aggregates in three ways: promoting, inhibiting, or binding to tau filaments. This reveals potential for diagnosing and treating neurodegenerative diseases like Alzheimer's.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Tau protein aggregation into fibrils is a hallmark of neurodegenerative diseases.
- Understanding small molecule interactions with tau is crucial for therapeutic development.
Purpose of the Study:
- To investigate the distinct modes of interaction between small molecules and tau monomers/aggregates.
- To identify small molecules with potential therapeutic or diagnostic applications in tauopathies.
Main Methods:
- High-throughput screening and other screening approaches.
- In vitro assays to study tau aggregation kinetics and binding affinities.
- Comparative analysis of small molecule selectivity against different protein aggregates.
Main Results:
- Anionic molecules (e.g., Congo red) promote tau filament formation at high concentrations (>10 µM).
- Ligands like cyanine dyes inhibit tau aggregation at low concentrations (<1 µM).
- Some compounds bind existing tau fibrils with high selectivity over amyloid-beta or alpha-synuclein aggregates.
Conclusions:
- Small molecules can modulate tau aggregation pathways through distinct mechanisms.
- Identified compounds show potential for modeling tauopathies, inhibiting disease pathology, and diagnostic imaging of neurofibrillary lesions.
