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Recent advances in cellular effects of fluoride: an update on its signalling pathway and targeted therapeutic approaches.Abstract
Fluoride is a natural element essential in minute quantities in human’s to maintain dental and skeletal health. However, the disease fluorosis manifests itself due to excessive fluoride intake mostly through drinking water and sometimes through food. At the cellular energetics level, fluoride is a known inhibitor of glycolysis. At the tissue level, the effect of fluoride has been more pronounced in the musculoskeletal systems due to its ability to retain fluoride. Fluoride alters dentinogenesis, thereby affecting the tooth enamel formation. In bones, fluoride alters the osteogenesis by replacing calcium, thus resulting in bone deformities. In skeletal muscles, high concentration and long term exposure to fluoride causes loss of muscle proteins leading to atrophy. Although fluorosis is quite a familiar problem, the exact molecular pathway is not yet clear. Extensive research on the effects of fluoride on various organs and its toxicity was reported. Indeed, it is clear that high and chronic exposure to fluoride causes cellular apoptosis. Accordingly, in this review, we have highlighted fluoride-mediated apoptosis via two vital pathways, mitochondrial-mediated and endoplasmic reticulum stress pathways. This review also elaborates on new cellular energetic, apoptotic pathways and therapeutic strategies targeted to treat fluorosis.
Graphic abstract
Keywords
- Fluoride
- Fluorosis
- Apoptosis
- Mitochondrial dysfunction
- Endoplasmic reticulum stress
- Therapeutic approaches
*Original abstract online at https://link.springer.com/article/10.1007%2Fs11033-021-06523-6#Fun
Abbreviations
- ATP: Adenosine triphosphate
- Caspase: Cysteine aspartate specific protease
- PARP: Poly (ADP-ribose) polymerase
- Cyt C: Cytochrome C
- ER: Endoplasmic reticulum
- Grp78: Glucose regulated protein 78
- MFN: Mitofusin
- MMP: Mitochondrial membrane potential
- ROS: Reactive oxygen species
- UPR: Unfolded protein response
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Acknowledgements
The authors would like to thank Dr.Shivashankara A.R., Associate Professor in Biochemistry, Father Muller Medical College, Mangalore, for his suggestions to improve the scientific content in this article. The authors would also like to thank Yenepoya Research Centre, Yenepoya Deemed to be University, for providing the online library resources for writing this perspective article.
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Nagendra, A.H., Bose, B. & Shenoy P, S. Recent advances in cellular effects of fluoride: an update on its signalling pathway and targeted therapeutic approaches. Mol Biol Rep (2021). https://doi.org/10.1007/s11033-021-06523-6
- Received03 March 2021
- Accepted25 June 2021
- Published12 July 2021
- DOIhttps://doi.org/10.1007/s11033-021-06523-6