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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

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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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AHN: Contributed in writing the paper and conceived the artwork. BB and SSP: Contributed in writing, correcting the text, finalizing the manuscript. All authors read and approved the manuscript.

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Correspondence to Bipasha Bose or Sudheer Shenoy P.

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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 48, 5661–5673 (2021). https://doi.org/10.1007/s11033-021-06523-6

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Keywords

  • Fluoride
  • Fluorosis
  • Apoptosis
  • Mitochondrial dysfunction
  • Endoplasmic reticulum stress
  • Therapeutic approaches