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Review
. 2023 Nov 13:17:3295-3323.
doi: 10.2147/DDDT.S380612. eCollection 2023.

The Role of Traditional Chinese Medicine Natural Products in β-Amyloid Deposition and Tau Protein Hyperphosphorylation in Alzheimer's Disease

Affiliations
Review

The Role of Traditional Chinese Medicine Natural Products in β-Amyloid Deposition and Tau Protein Hyperphosphorylation in Alzheimer's Disease

Huiying Yan et al. Drug Des Devel Ther. .

Abstract

Alzheimer's disease is a prevalent form of dementia among elderly individuals and is characterized by irreversible neurodegeneration. Despite extensive research, the exact causes of this complex disease remain unclear. Currently available drugs for Alzheimer's disease treatment are limited in their effectiveness, often targeting a single aspect of the disease and causing significant adverse effects. Moreover, these medications are expensive, placing a heavy burden on patients' families and society as a whole. Natural compounds and extracts offer several advantages, including the ability to target multiple pathways and exhibit high efficiency with minimal toxicity. These attributes make them promising candidates for the prevention and treatment of Alzheimer's disease. In this paper, we provide a summary of the common natural products used in Chinese medicine for different pathogeneses of AD. Our aim is to offer new insights and ideas for the further development of natural products in Chinese medicine and the treatment of AD.

Keywords: Alzheimer’s disease; Chinese herbal medicine; natural products; review; tau-protein hyperphosphorylation; β-amyloid deposition.

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Conflict of interest statement

The authors report no conflicts of interest associated with this publication.

Figures

Figure 1
Figure 1
How extracellular β-amyloid deposition occurs. Amyloid precursor protein (APP) is cleaved by β-secretase to produce the transmembrane 99-residue C-terminal fragment (C99). This C99 fragment is then processed by γ-secretase, leading to the release of the amyloid precursor protein intracellular domain (AICD) into the cytoplasm.
Figure 2
Figure 2
Schematic representation of the PI3K/AKT/GSK-3β-mediated phosphorylation signaling pathway and its role in autophagy in AD. Endosomes are membrane-enclosed organelles found in animal cells. Their primary function is to transport substances that are newly ingested through endocytosis to lysosomes, where they are degraded.
Figure 3
Figure 3
Diagram of the association between the breakdown of the BBB and AD.
Figure 4
Figure 4
Schematic representation of disease-associated phosphorylation sites in tau. (A) The distribution of tau phosphorylation sites in Homo sapiens (441 aa CNS isoform) was determined by mass spectrometry of PHF tau. Different tau regions are indicated in various colors, with major phosphorylation sites shown in yellow. (B) Schematic representation of splice isoforms of tau in the CNS is provided, with alternatively spliced exons indicated as red boxes. The vertical red lines on top represent the phosphorylation sites listed in (A). Reprinted from Trushina NI, Bakota L, Mulkidjanian AY et al. The Evolution of Tau Phosphorylation and Interactions. Front Aging Neurosci. 2019;11:256. Creative Commons.
Figure 5
Figure 5
Deregulation of PP2A-tau protein–protein interactions in AD. ((A) The PP2A/Bα holoenzyme has the ability to directly interact with human tau isoforms that have three or four repeats. This interaction occurs through a domain that includes the microtubule-binding repeats, leading to the dephosphorylation of tau. A crucial role in regulating the protein‒protein interactions between PP2A and tau is played by a specific proline-rich motif that contains the Thr231 phosphorylation site. (B) The PP2A-Tau protein‒protein interaction can be inhibited in vitro by these six methods). Adapted from Sontag JM, Sontag E. Protein phosphatase 2A dysfunction in Alzheimer’s disease. Front Mol Neurosci. 2014;7. Creative Commons.
Figure 6
Figure 6
Microglia may be critical intermediaries of Aβ–tau synergy.

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Grants and funding

Education Department of Jilin Province “13th Five-Year” science and technology project (JJKH20200895KJ); Science and technology ability promotion Plan of Health Commission of Jilin Province (2019J058); Jilin Provincial Science and Technology Department key research and development-medicine and health field (20200404065YY); Natural Science Foundation of Shandong (ZR2023QH159).