Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jan 9;25(2):831.
doi: 10.3390/ijms25020831.

Modulation of Tau Pathology in Alzheimer's Disease by Dietary Bioactive Compounds

Huahua Shi  1   2 , Yan Zhao  1   2
Affiliations
Review

Modulation of Tau Pathology in Alzheimer's Disease by Dietary Bioactive Compounds

Huahua Shi et al. Int J Mol Sci. .

Abstract

Tau is a microtubule-associated protein essential for microtubule assembly and stability in neurons. The abnormal intracellular accumulation of tau aggregates is a major characteristic of brains from patients with Alzheimer's disease (AD) and other tauopathies. In AD, the presence of neurofibrillary tangles (NFTs), which is composed of hyperphosphorylated tau protein, is positively correlated with the severity of the cognitive decline. Evidence suggests that the accumulation and aggregation of tau cause synaptic dysfunction and neuronal degeneration. Thus, the prevention of abnormal tau phosphorylation and elimination of tau aggregates have been proposed as therapeutic strategies for AD. However, currently tau-targeting therapies for AD and other tauopathies are limited. A number of dietary bioactive compounds have been found to modulate the posttranslational modifications of tau, including phosphorylation, small ubiquitin-like modifier (SUMO) mediated modification (SUMOylation) and acetylation, as well as inhibit tau aggregation and/or promote tau degradation. The advantages of using these dietary components over synthetic substances in AD prevention and intervention are their safety and accessibility. This review summarizes the mechanisms leading to tau pathology in AD and highlights the effects of bioactive compounds on the hyperphosphorylation, aggregation and clearance of tau protein. The potential of using these bioactive compounds for AD prevention and intervention is also discussed.

Keywords: Alzheimer’s disease; dietary bioactive compounds; tau pathology.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The human tau gene and tau isoforms. In adult human brain, tau gene encodes six tau isoforms 4R/2N, 4R/1N, 3R/2N, 4R/0N, 3R/1N and 3R/0N, which are generated from alternative splicing of exons 2, 3, and 10. “R” indicates microtubule-associated-binding repeat; “N” represents the N-terminal inserts.
Figure 2
Figure 2
Tau phosphorylation in physiological condition and pathological state. (a) Tau regulates microtubule stability and dynamics in human neurons by directly binding to microtubules. The microtubule-binding repeats of tau protein bind at the inner face of the microtubules while the proline-rich region interacts with the surface of the microtubules. The interaction of tau with microtubules is regulated by phosphorylation via the concerted action of a variety of kinases and phosphatases. (b) In the pathological state, tau is hyperphosphorylated and no longer binds to microtubules, contributing to axonal dysfunction, and driving its oligomerization and aggregation into larger order insoluble fibrils.
Figure 3
Figure 3
Possible protective mechanisms of bioactive compounds against tau pathology in AD.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Tapia-Rojas C., Cabezas-Opazo F., Deaton C.A., Vergara E.H., Johnson G.V.W., Quintanilla R.A. It’s all about tau. Prog. Neurobiol. 2019;175:54–76. doi: 10.1016/j.pneurobio.2018.12.005. - DOI - PMC - PubMed
    1. Xia Y.X., Prokop S., Giasson B.I. “Don’t Phos Over Tau”: Recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies. Mol. Neurodegener. 2021;16:19. doi: 10.1186/s13024-021-00460-5. - DOI - PMC - PubMed
    1. Rawat P., Sehar U., Bisht J., Selman A., Culberson J., Reddy P.H. Phosphorylated Tau in Alzheimer’s Disease and Other Tauopathies. Int. J. Mol. Sci. 2022;23:12841. doi: 10.3390/ijms232112841. - DOI - PMC - PubMed
    1. Arakhamia T., Lee C.E., Carlomagno Y., Duong D.M., Kundinger S.R., Wang K., Williams D., DeTure M., Dickson D.W., Cook C.N., et al. Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains. Cell. 2020;180:633–644. doi: 10.1016/j.cell.2020.01.027. - DOI - PMC - PubMed
    1. Martin L., Latypova X., Terro F. Post-translational modifications of tau protein: Implications for Alzheimer’s disease. Neurochem. Int. 2011;58:458–471. doi: 10.1016/j.neuint.2010.12.023. - DOI - PubMed

LinkOut - more resources