Related Experiment Video
Updated: Dec 13, 2025
Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes
Published on: December 20, 2019
Modulating disease-relevant tau oligomeric strains by small molecules.
Filippa Lo Cascio1, Stephanie Garcia1, Mauro Montalbano1
1Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, Texas, USA; Departments of Neurology, Neuroscience, and Cell Biology, University of Texas Medical Branch, Galveston, Texas, USA.
Novel curcumin derivatives, like CL3, reduce the toxicity of tau oligomers in brain-derived tau oligomers (BDTOs). These compounds reshape toxic aggregates into less harmful forms, offering therapeutic potential for tauopathies.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Pathological tau aggregation is central to neurodegenerative tauopathies.
- Tau oligomers are highly toxic, seeding misfolding and disease propagation.
- Curcumin derivatives previously showed potential in modulating tau aggregation.
Purpose of the Study:
- To investigate the therapeutic potential of curcumin derivatives on brain-derived tau oligomers (BDTOs) from various tauopathies.
- To determine if these compounds can modulate BDTO aggregation and reduce neurotoxicity.
- To explore compound CL3's specific effects on BDTOs and their properties.
Main Methods:
- Utilized well-characterized BDTOs isolated from human brain tissues of Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies.
- Assessed the effects of curcumin derivatives on BDTO aggregation state, neurotoxicity, hydrophobicity, and seeding propensity.
- Characterized the resulting tau aggregates formed in the presence of the compounds.
Main Results:
- Curcumin derivatives modulated BDTO aggregation, reshaping them into larger, less toxic tau aggregates.
- Compound CL3 demonstrated efficacy across BDTOs from different tauopathies.
- CL3-treated BDTOs exhibited decreased hydrophobicity and seeding propensity, rescuing neurons from toxicity.
Conclusions:
- Curcumin derivatives, particularly CL3, show therapeutic promise for tauopathies by reducing tau oligomer toxicity.
- CL3's ability to modulate BDTO aggregation and neurotoxicity supports its potential for treating tauopathies.
- CL3 may also serve as a basis for developing diagnostic imaging agents for tauopathies.
