The aggregates of
microtubule-associated protein Tau are considered as a major hallmark of
Alzheimer's disease. Tau aggregates accumulate intracellularly leading to neuronal toxicity. Numerous approaches have been targeted against
Tau protein aggregation, which include application of synthetic and natural compounds.
Toluidine blue is a basic
dye of
phenothiazine family, which on irradiation with a 630 nm light gets converted into a photoexcited form, leading to generation of
singlet oxygen species.
Methylene blue is the parent compound of
toluidine blue, which has been reported to be potent against
tauopathy. In the present work, we studied the potency of
toluidine blue and photoexcited
toluidine blue against Tau aggregation. Biochemical and biophysical analyses using
sodium dodecyl sulfate-
polyacrylamide gel electrophoresis, ThS fluorescence, circular dichroism spectroscopy, and electron microscopy suggested that
toluidine blue inhibited the aggregation of Tau in vitro. The photoexcited
toluidine blue potentially dissolved the matured Tau fibrils, which indicated the disaggregation property of
toluidine blue. The cell biology studies including the cytotoxicity assay and
reactive oxygen species (ROS) production assay suggested
toluidine blue to be a biocompatible
dye as it reduced ROS levels and cell death. The photoexcited
toluidine blue modulates the cytoskeleton network in cells, which was supported by immunofluorescence studies of neuronal cells. The studies in a UAS Tau E14 transgenic Drosophila model suggested that photoexcited
toluidine blue was potent to restore the survival and
memory deficits of Drosophila. The overall finding of our studies suggested
toluidine blue to be a potent molecule in rescuing the Tau-mediated pathology by inhibiting its aggregation, reducing the cell death, and modulating the
tubulin levels and behavioral characteristics of Drosophila. Thus,
toluidine blue can be addressed as a potent molecule against
Alzheimer's disease.