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Published on: November 9, 2018
Methylene blue reduced abnormal tau accumulation in P301L tau transgenic mice
Masato Hosokawa1, Tetsuaki Arai, Masami Masuda-Suzukake
1Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Abstract:
In neurodegenerative disorders, abnormally hyperphosphorylated and aggregated tau accumulates intracellularly, a mechanism which is thought to induce neuronal cell death. Methylene blue, a type of phenothiazine, has been reported to inhibit tau aggregation in vitro. However, the effect of methylene blue in vivo has remained unknown. Therefore, we examined whether methylene blue suppresses abnormal tau accumulation using P301L tau transgenic mice. At 8 to 11 months of age, these mice were orally administered methylene blue for 5 months. Subsequent results of Western blotting analysis revealed that this agent reduced detergent-insoluble phospho-tau. Methylene blue may have potential as a drug candidate for the treatment of tauopathy.
Insights
Methylene blue, a phenothiazine, was tested in P301L tau transgenic mice to see if it could reduce abnormal tau accumulation. The study found that methylene blue significantly reduced insoluble phospho-tau, suggesting its potential for treating tauopathies.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Neurodegenerative disorders involve intracellular accumulation of hyperphosphorylated and aggregated tau, leading to neuronal cell death.
- Methylene blue, a phenothiazine derivative, has demonstrated in vitro inhibition of tau aggregation.
- The in vivo efficacy of methylene blue in preventing tau pathology remained uninvestigated.
Purpose of the Study:
- To investigate the in vivo effect of methylene blue on the suppression of abnormal tau accumulation.
- To evaluate methylene blue as a potential therapeutic agent for tauopathies.
Main Methods:
- Administration of methylene blue to P301L tau transgenic mice over a 5-month period.
- Utilizing Western blotting analysis to quantify detergent-insoluble phospho-tau levels.
Main Results:
- Methylene blue administration significantly reduced detergent-insoluble phospho-tau in P301L tau transgenic mice.
- The observed reduction in abnormal tau suggests a therapeutic effect of methylene blue in vivo.
Conclusions:
- Methylene blue demonstrates efficacy in suppressing abnormal tau accumulation in a mouse model of tauopathy.
- Methylene blue shows potential as a drug candidate for treating neurodegenerative diseases characterized by tau pathology, such as Alzheimer's disease.
