Methylene blue reduced abnormal tau accumulation in P301L tau transgenic mice

PLoS One. 2012;7(12):e52389. doi: 10.1371/journal.pone.0052389. Epub 2012 Dec 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution*
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Immunoblotting
  • Immunohistochemistry
  • Methylene Blue / pharmacology*
  • Mice
  • Mice, Transgenic
  • Mutant Proteins / chemistry
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism*
  • Phosphorylation / drug effects
  • Protein Structure, Quaternary
  • Sarcosine / analogs & derivatives
  • Sarcosine / pharmacology
  • Solubility
  • Subcellular Fractions / metabolism
  • tau Proteins / chemistry
  • tau Proteins / genetics*
  • tau Proteins / metabolism*

Substances

  • Mutant Proteins
  • tau Proteins
  • sarkosyl
  • Methylene Blue
  • Sarcosine

Grant support

This research was partially supported by the Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research (C), grant number 21591536 to HA and 24591738 to M. Hosokawa. The additional part of the funding of the authors′ study has come from institute budget. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.