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Anionic micelles and vesicles induce tau fibrillization in vitro
Carmen N Chirita1, Mihaela Necula, Jeff Kuret
1Biophysics Program and Department of Molecular and Cellular Biochemistry, The Ohio State University College of Medicine and Public Health, Columbus, Ohio 43210, USA.
The Journal of Biological Chemistry
|May 6, 2003
Summary
Fatty acids with long alkyl chains and negative charges induce tau protein fibrillization, a key process in Alzheimer's disease. Anionic surfaces, like micelles or vesicles, are crucial for initiating this tau filament formation.
Area of Science:
- Neuroscience
- Biochemistry
- Molecular Biology
Background:
- Alzheimer's disease (AD) is characterized by intraneuronal tau protein filaments.
- Tau fibrillization can be induced in vitro by various agents, including fatty acids.
Purpose of the Study:
- To characterize the structural requirements of fatty acids that induce tau fibrillization.
- To investigate the role of anionic surfaces in tau filament formation.
Main Methods:
- Used recombinant full-length tau protein and arachidonic acid.
- Tested straight-chain anionic, cationic, and nonionic detergents.
- Investigated tau fibrillization induced by phosphatidylserine vesicles.
Main Results:
- Tau fibrillization required a minimum alkyl chain length of 12 carbons and a negative charge (carboxylate, sulfonate, or sulfate).
- Active fatty acids and detergents formed micelles, with tau-dependent depression of critical micelle concentrations.
- Anionic surfaces, including vesicles, nucleated tau fibrillization.
Conclusions:
- Anionic surfaces, presented as micelles or vesicles, can nucleate tau fibrillization.
- This mechanism explains the activity of fatty acid inducers of tau aggregation.
- Anionic membranes may play a role in tau fibrillization in vivo.