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.
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