Mechanisms of Tau Protein in Alzheimer’s Disease Pathogenesis and Potential Therapeutic Strategies: A Brief Review

Research Article
Open access

Mechanisms of Tau Protein in Alzheimer’s Disease Pathogenesis and Potential Therapeutic Strategies: A Brief Review

Shunyao Xu 1*
  • 1 Southern Medical University, Guangzhou, China, 510515    
  • *corresponding author Leonardoxvsy@outlook.com
TNS Vol.117
ISSN (Print): 2753-8826
ISSN (Online): 2753-8818
ISBN (Print): 978-1-80590-199-0
ISBN (Online): 978-1-80590-200-3

Abstract

Under normal physiological conditions, tau protein can maintain the function of microtubules, while under pathological conditions, it dissociates from microtubules and aggregates, thereby disrupting microtubule function and ultimately leading to neuronal damage and the development of neurodegenerative diseases. Under pathological conditions, tau protein undergoes modifications such as phosphorylation, acetylation, ubiquitination, and truncation. These changes lead to the formation of neurofibrillary tangles through various mechanisms and ultimately cause Alzheimer's disease. In response to these diverse pathogenic mechanisms, people have developed a variety of potential therapeutic approaches targeting the underlying causes, such as modulating autophagy, inhibiting tau protein aggregation, clearing tau protein and so on. These studies demonstrate that the progression of neurodegenerative diseases, headed by Alzheimer's disease (AD), can be inhibited. This article aims to discuss the limitations in the aforementioned mechanisms and their corresponding therapeutic approaches, and to explore whether there are methods and ideas to address these shortcomings. Regrettably, the current potential therapeutic approaches are still unable to completely cure Alzheimer's disease, and the conditions required for treatment are rather demanding. However, these therapeutic methods may potentially serve as means for the early diagnosis and prevention of Alzheimer's disease. This article may provide more ideas for new therapeutic approaches to AD and other neurodegenerative diseases.

Keywords:

Tau protein, Alzheimer’s disease, function, post-translational modification, treatment

Xu,S. (2025). Mechanisms of Tau Protein in Alzheimer’s Disease Pathogenesis and Potential Therapeutic Strategies: A Brief Review. Theoretical and Natural Science,117,1-7.
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References

[1]. Scheltens P., De Strooper B., Kivipelto M., Holstege H., Chételat G., Teunissen C.E., Cummings J., van der Flier W.M. Alzheimer's disease. Lancet. 2021 Apr 24;397(10284):1577-1590.

[2]. Drubin D.G., Kirschner M.W. Tau protein function in living cells. J Cell Biol. 1986 Dec;103(6 Pt 2):2739-46. doi: 10.1083/jcb.103.6.2739.

[3]. Guo T., Noble W., Hanger D.P. Roles of tau protein in health and disease. Acta Neuropathol. 2017 May;133(5):665-704. doi: 10.1007/s00401-017-1707-9.

[4]. Šimić G., Babić Leko M., Wray S., et al. Tau Protein Hyperphosphorylation and Aggregation in Alzheimer's Disease and Other Tauopathies, and Possible Neuroprotective Strategies. Biomolecules. 2016 Jan 6;6(1):6. doi: 10.3390/biom6010006.

[5]. Park S., Lee J.H., Jeon J.H., Lee M.J. Degradation or aggregation: the ramifications of post-translational modifications on tau. BMB Rep. 2018 Jun;51(6):265-273.

[6]. Hamano T., Enomoto S., Shirafuji N., Ikawa M., Yamamura O., Yen S.H., Nakamoto Y. Autophagy and Tau Protein. Int J Mol Sci. 2021 Jul 12;22(14):7475. doi: 10.3390/ijms22147475.

[7]. Iqbal K., Liu F., Gong C.X., Alonso Adel C., Grundke-Iqbal I. Mechanisms of tau-induced neurodegeneration. Acta Neuropathol. 2009 Jul;118(1):53-69. doi: 10.1007/s00401-009-0486-3.

[8]. Kuang H., Tan C.Y., Tian H.Z., Liu L.H., Yang M.W., Hong F.F., Yang S.L. Exploring the bi-directional relationship between autophagy and Alzheimer's disease. CNS Neurosci Ther. 2020 Feb;26(2):155-166.

[9]. A. Boutajangout, E.M. Sigurdsson, P.K. Krishnamurthy. Tau as a Therapeutic Target for Alzheimer's Disease [J]. Current Alzheimer research, 2011(6):8.

[10]. Passeri E., Elkhoury K., Morsink M., Broersen K., Linder M., Tamayol A., Malaplate C., Yen F. T., Arab-Tehrany E. Alzheimer's Disease: Treatment Strategies and Their Limitations. Int J Mol Sci. 2022 Nov 12;23(22):13954.

[11]. Sigurdsson E M. Immunotherapy targeting pathological tau protein in Alzheimer's disease and related tauopathies. J Alzheimers Dis. 2008 Oct;15(2):157-68.

[12]. Breijyeh Z., Karaman R. Comprehensive Review on Alzheimer's Disease: Causes and Treatment. Molecules. 2020 Dec 8;25(24):5789.

Cite this article

Xu,S. (2025). Mechanisms of Tau Protein in Alzheimer’s Disease Pathogenesis and Potential Therapeutic Strategies: A Brief Review. Theoretical and Natural Science,117,1-7.

Data availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

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About volume

Volume title: Proceedings of ICBioMed 2025 Symposium: Computational Modelling and Simulation for Biology and Medicine

ISBN：978-1-80590-199-0(Print) / 978-1-80590-200-3(Online)
Editor：Alan Wang, Roman Bauer
Conference website: https://www.icbiomed.org/london.html
Conference date: 19 September 2025
Series: Theoretical and Natural Science
Volume number: Vol.117
ISSN：2753-8818(Print) / 2753-8826(Online)

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References

[1]. Scheltens P., De Strooper B., Kivipelto M., Holstege H., Chételat G., Teunissen C.E., Cummings J., van der Flier W.M. Alzheimer's disease. Lancet. 2021 Apr 24;397(10284):1577-1590.

[2]. Drubin D.G., Kirschner M.W. Tau protein function in living cells. J Cell Biol. 1986 Dec;103(6 Pt 2):2739-46. doi: 10.1083/jcb.103.6.2739.

[3]. Guo T., Noble W., Hanger D.P. Roles of tau protein in health and disease. Acta Neuropathol. 2017 May;133(5):665-704. doi: 10.1007/s00401-017-1707-9.

[4]. Šimić G., Babić Leko M., Wray S., et al. Tau Protein Hyperphosphorylation and Aggregation in Alzheimer's Disease and Other Tauopathies, and Possible Neuroprotective Strategies. Biomolecules. 2016 Jan 6;6(1):6. doi: 10.3390/biom6010006.

[5]. Park S., Lee J.H., Jeon J.H., Lee M.J. Degradation or aggregation: the ramifications of post-translational modifications on tau. BMB Rep. 2018 Jun;51(6):265-273.

[6]. Hamano T., Enomoto S., Shirafuji N., Ikawa M., Yamamura O., Yen S.H., Nakamoto Y. Autophagy and Tau Protein. Int J Mol Sci. 2021 Jul 12;22(14):7475. doi: 10.3390/ijms22147475.

[7]. Iqbal K., Liu F., Gong C.X., Alonso Adel C., Grundke-Iqbal I. Mechanisms of tau-induced neurodegeneration. Acta Neuropathol. 2009 Jul;118(1):53-69. doi: 10.1007/s00401-009-0486-3.

[8]. Kuang H., Tan C.Y., Tian H.Z., Liu L.H., Yang M.W., Hong F.F., Yang S.L. Exploring the bi-directional relationship between autophagy and Alzheimer's disease. CNS Neurosci Ther. 2020 Feb;26(2):155-166.

[9]. A. Boutajangout, E.M. Sigurdsson, P.K. Krishnamurthy. Tau as a Therapeutic Target for Alzheimer's Disease [J]. Current Alzheimer research, 2011(6):8.

[10]. Passeri E., Elkhoury K., Morsink M., Broersen K., Linder M., Tamayol A., Malaplate C., Yen F. T., Arab-Tehrany E. Alzheimer's Disease: Treatment Strategies and Their Limitations. Int J Mol Sci. 2022 Nov 12;23(22):13954.

[11]. Sigurdsson E M. Immunotherapy targeting pathological tau protein in Alzheimer's disease and related tauopathies. J Alzheimers Dis. 2008 Oct;15(2):157-68.

[12]. Breijyeh Z., Karaman R. Comprehensive Review on Alzheimer's Disease: Causes and Treatment. Molecules. 2020 Dec 8;25(24):5789.

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