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Nontoxic singlet oxygen generator as a therapeutic candidate for treating tauopathies

Sahabudeen Sheik Mohideen1, Yasutoyo Yamasaki2, Yasuhiro Omata3

  • 1Alzheimer's Disease Project Team, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, Japan 474-8511.

Scientific Reports
|June 2, 2015
PubMed

Insights

Methylene blue (MB) reduces tau aggregation in flies but has toxic effects. Singlet oxygen generators, like rose bengal, show promise for treating tauopathies with less toxicity.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Genetics

Background:

  • Neurofibrillary tangles, primarily composed of tau protein, are hallmarks of tauopathies.
  • Methylene blue (MB) is known to inhibit tau aggregation, but its in vivo mechanisms and effects remain unclear.

Purpose of the Study:

  • To investigate the in vivo mechanism of Methylene blue (MB) in reducing tau aggregation.
  • To evaluate the therapeutic potential and toxicity of MB and other singlet oxygen generators in a Drosophila model of tauopathy.

Main Methods:

  • Utilized Drosophila melanogaster models expressing human wild-type tau.
  • Administered Methylene blue (MB) and rose bengal (RB) treatments.
  • Assessed sarkosyl-insoluble tau levels, climbing behavior, and survival rates.

Main Results:

  • MB treatment decreased sarkosyl-insoluble tau and partially improved climbing deficits in transgenic flies.
  • MB diminished climbing activity and survival rates in wild-type flies, suggesting photosensitive toxicity via singlet oxygen.
  • Rose bengal (RB) suppressed tau accumulation and behavioral deficits with reduced toxicity compared to MB.

Conclusions:

  • Singlet oxygen generation by MB contributes to both its beneficial and toxic effects in vivo.
  • Drug candidates generating singlet oxygen with minimal toxicity are promising for tauopathy treatment.
  • Further research into photosensitive compounds for tauopathies is warranted.

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