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

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          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.

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          Most cited references169

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          The amyloid hypothesis of Alzheimer's disease at 25 years

          Abstract Despite continuing debate about the amyloid β‐protein (or Aβ hypothesis, new lines of evidence from laboratories and clinics worldwide support the concept that an imbalance between production and clearance of Aβ42 and related Aβ peptides is a very early, often initiating factor in Alzheimer's disease (AD). Confirmation that presenilin is the catalytic site of γ‐secretase has provided a linchpin: all dominant mutations causing early‐onset AD occur either in the substrate (amyloid precursor protein, APP) or the protease (presenilin) of the reaction that generates Aβ. Duplication of the wild‐type APP gene in Down's syndrome leads to Aβ deposits in the teens, followed by microgliosis, astrocytosis, and neurofibrillary tangles typical of AD. Apolipoprotein E4, which predisposes to AD in > 40% of cases, has been found to impair Aβ clearance from the brain. Soluble oligomers of Aβ42 isolated from AD patients' brains can decrease synapse number, inhibit long‐term potentiation, and enhance long‐term synaptic depression in rodent hippocampus, and injecting them into healthy rats impairs memory. The human oligomers also induce hyperphosphorylation of tau at AD‐relevant epitopes and cause neuritic dystrophy in cultured neurons. Crossing human APP with human tau transgenic mice enhances tau‐positive neurotoxicity. In humans, new studies show that low cerebrospinal fluid (CSF) Aβ42 and amyloid‐PET positivity precede other AD manifestations by many years. Most importantly, recent trials of three different Aβ antibodies (solanezumab, crenezumab, and aducanumab) have suggested a slowing of cognitive decline in post hoc analyses of mild AD subjects. Although many factors contribute to AD pathogenesis, Aβ dyshomeostasis has emerged as the most extensively validated and compelling therapeutic target.
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            Wnt/β-catenin signaling and disease.

            The WNT signal transduction cascade controls myriad biological phenomena throughout development and adult life of all animals. In parallel, aberrant Wnt signaling underlies a wide range of pathologies in humans. In this Review, we provide an update of the core Wnt/β-catenin signaling pathway, discuss how its various components contribute to disease, and pose outstanding questions to be addressed in the future. Copyright © 2012 Elsevier Inc. All rights reserved.
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              2021 Alzheimer's disease facts and figures

              (2021)
              This article describes the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality and morbidity, use and costs of care, and the overall impact on caregivers and society. The Special Report discusses the challenges of providing equitable health care for people with dementia in the United States. An estimated 6.2 million Americans age 65 and older are living with Alzheimer's dementia today. This number could grow to 13.8 million by 2060 barring the development of medical breakthroughs to prevent, slow or cure AD. Official death certificates recorded 121,499 deaths from AD in 2019, the latest year for which data are available, making Alzheimer's the sixth-leading cause of death in the United States and the fifth-leading cause of death among Americans age 65 and older. Between 2000 and 2019, deaths from stroke, heart disease and HIV decreased, whereas reported deaths from AD increased more than 145%. This trajectory of deaths from AD was likely exacerbated in 2020 by the COVID-19 pandemic. More than 11 million family members and other unpaid caregivers provided an estimated 15.3 billion hours of care to people with Alzheimer's or other dementias in 2020. These figures reflect a decline in the number of caregivers compared with a decade earlier, as well as an increase in the amount of care provided by each remaining caregiver. Unpaid dementia caregiving was valued at $256.7 billion in 2020. Its costs, however, extend to family caregivers' increased risk for emotional distress and negative mental and physical health outcomes - costs that have been aggravated by COVID-19. Average per-person Medicare payments for services to beneficiaries age 65 and older with AD or other dementias are more than three times as great as payments for beneficiaries without these conditions, and Medicaid payments are more than 23 times as great. Total payments in 2021 for health care, long-term care and hospice services for people age 65 and older with dementia are estimated to be $355 billion. Despite years of efforts to make health care more equitable in the United States, racial and ethnic disparities remain - both in terms of health disparities, which involve differences in the burden of illness, and health care disparities, which involve differences in the ability to use health care services. Blacks, Hispanics, Asian Americans and Native Americans continue to have a higher burden of illness and lower access to health care compared with Whites. Such disparities, which have become more apparent during COVID-19, extend to dementia care. Surveys commissioned by the Alzheimer's Association recently shed new light on the role of discrimination in dementia care, the varying levels of trust between racial and ethnic groups in medical research, and the differences between groups in their levels of concern about and awareness of Alzheimer's disease. These findings emphasize the need to increase racial and ethnic diversity in both the dementia care workforce and in Alzheimer's clinical trials.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                13 November 2023
                2023
                : 17
                : 3295-3323
                Affiliations
                [1 ]Department of Neurology, the Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine , Changchun, Jilin Province, People’s Republic of China
                [2 ]Shandong Key Laboratory of TCM Multi-Targets Intervention and Disease Control, the Second Affiliated Hospital of Shandong First Medical University , Taian, Shandong Province, People’s Republic of China
                Author notes
                Correspondence: Lina Feng, The Second Affiliated Hospital of Shandong First Medical University , Yingsheng Road 2, Taian, Shandong Province, 271000, People’s Republic of China, Tel +86-15543120222, Email fenglina0001@163.com
                Mingquan Li, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine , Boshuo Road, Changchun, Jilin, 130117, People’s Republic of China, Tel +86-15948000577, Email Limingquan0001@126.com
                Author information
                http://orcid.org/0009-0006-3038-7930
                Article
                380612
                10.2147/DDDT.S380612
                10655607
                f82b6fb9-7c2a-4fba-b174-98dcd48d483f
                © 2023 Yan et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 14 August 2023
                : 02 November 2023
                Page count
                Figures: 6, Tables: 2, References: 169, Pages: 29
                Funding
                Funded by: Education Department of Jilin Province, open-funder-registry 10.13039/501100010211;
                Funded by: Science and technology ability promotion Plan of Health Commission of Jilin Province;
                Funded by: Jilin Provincial Science and Technology Department key research and development-medicine and health field;
                Funded by: Natural Science Foundation of Shandong, open-funder-registry 10.13039/501100007129;
                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).
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                alzheimer’s disease,β-amyloid deposition,tau-protein hyperphosphorylation,natural products,chinese herbal medicine,review

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