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Turkish Journal of Biology

Abstract

Background/aim: Tau protein, which is crucial for sustaining the cytoskeletal network by assisting microtubule construction, contributes significantly to the pathophysiology of Alzheimer’s disease (AD). The hyperphosphorylation of tau causes it to detach from microtubules (MTs), leading to the formation of neurofibrillary tangles (NFTs) in neurons, which ultimately results in cell death. Thionine (TH), a cationic phenothiazine-structured compound, has been the topic of extensive research due to its interesting physicochemical properties. It is a common biological dye, especially useful in histology due to its strong affinity for biological membranes. Furthermore, TH serves as a photosensitizer in phototherapy. It has a phenothiazine pharmacophore, which makes it selective against microbial and tumor cells. Our prior studies demonstrated that TH inhibits human plasma butyrylcholinesterase (BChE) by acting as a nonlinear inhibitor and also affects amyloid precursor protein (APP) metabolism in PS70 cells. In the current research, we investigated whether TH modulates the phosphorylation of tau in N2a/APPSwe cells.

Materials and methods: Using flow cytometry, we identified the dose range and treatment time of TH that did not affect the viability of N2a/APPSwe cells. The western blot method was used to investigate the effects of TH on total tau and four key tau phosphorylation sites.

Results: The results indicated that TH reduces tau phosphorylation at residues Ser202/Thr205, Ser396, Ser396/Ser404, and Thr181, which contribute to NFT formation.

Conclusion: When all these findings are evaluated together, TH may have a therapeutic potential against AD.

Author ORCID Identifier

SEDA ÖNDER: 0000-0002-0392-7077

KEVSER BİBEROĞLU: 0000-0001-9285-0819

ÖZDEN TACAL: 0000-0002-2772-5226

DOI

10.55730/1300-0152.2756

Keywords

Thionine, phenothiazine compounds, Alzheimer's disease, tau phosphorylation, neurofibrillary tangles

First Page

400

Last Page

408

Publisher

The Scientific and Technological Research Council of Türkiye (TÜBİTAK)

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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