[1]赵郑琪琦,刘 佳.维生素D减少阿尔茨海默病患者脑β-淀粉样蛋白沉积和抑制Tau蛋白磷酸化作用机制研究进展[J].现代检验医学杂志,2025,40(03):203-207.[doi:10.3969/j.issn.1671-7414.2025.03.038]
 ZHAO Zhengqiqi,LIU Jia.Research Progress on the Mechanism of Vitamin D Reducing β-amyloid Deposition and Inhibiting Tau Phosphorylation in Patients with Alzheimer’s Disease[J].Journal of Modern Laboratory Medicine,2025,40(03):203-207.[doi:10.3969/j.issn.1671-7414.2025.03.038]
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维生素D减少阿尔茨海默病患者脑β-淀粉样蛋白沉积和抑制Tau蛋白磷酸化作用机制研究进展()

《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年03期
页码:
203-207
栏目:
综述
出版日期:
2025-05-15

文章信息/Info

Title:
Research Progress on the Mechanism of Vitamin D Reducing β-amyloid Deposition and Inhibiting Tau Phosphorylation in Patients with Alzheimer’s Disease
文章编号:
1671-7414(2025)03-203-05
作者:
赵郑琪琦刘 佳
(首都医科大学燕京医学院,北京 101300)
Author(s):
ZHAO ZhengqiqiLIU Jia
(Yanjing Medical College, Capital Medical University, Beijing 101300, China)
关键词:
维生素D阿尔茨海默病β-淀粉样蛋白神经纤维缠结
分类号:
R749.16;Q565
DOI:
10.3969/j.issn.1671-7414.2025.03.038
文献标志码:
A
摘要:
阿尔茨海默病(AD)是一种致命的神经退行性疾病,通常伴随着进行性的记忆力减退、自理水平下降等症状。近年研究发现,维生素D(VD)可有效逆转AD患者脑内β-淀粉样蛋白(Aβ)沉积和Tau蛋白过度磷酸化现象,并明显改善AD的记忆力衰退症状。该文从Aβ沉积和Tau磷酸化两个层面总结VD治疗AD机制,以期为AD患者提供潜在的治疗靶点。
Abstract:
Alzheimer’s disease (AD) is a fatal neurodegenerative disorder, typically characterized by progressive memory impairment, diminished self-care abilities, and other associated symptoms. Recent studies have demonstrated the potential of Vitamin D (VD) in effectively mitigating amyloid β-protein deposition and Tau protein hyperphosphorylation in the brains of AD patients, leading to significant improvements in memory decline. In this study, the authors elucidate the mechanisms underlying the therapeutic effects of Vitamin D in Alzheimer’s disease (AD), focusing on its impact on Aβ deposition and Tau phosphorylation. Additionally, potential therapeutic targets for AD patients are proposed based on these findings.

参考文献/References:

[1] SCHELTENS P, DE STROOPER B, KIVIPELTO M, et al. Alzheimer’s disease[J]. Lancet (London, England), 2021, 397(10284): 1577-1590.
[2] BHATT J , HERRERA A C , AMICO F D ,et al. The world Alzheimer report 2019: attitudes to dementia[EB/OL]. https://www.researchgate.net/publication/335927874_The_World_Alzheimer_Report_2019_Attitudes_to_dementia.
[3] JAYEDI A, RASHIDY-POUR A, SHAB-BIDAR S. Vitamin D status and risk of dementia and Alzheimer’s disease: a meta-analysis of dose-response[J]. Nutritional Neuroscience, 2019, 22(11): 750-759.
[4] BEATA B K, WOJCIECH J, JOHANNES K, et al. Alzheimer’s disease-biochemical and psychological background for diagnosis and treatment[J]. International Journal of Molecular Sciences, 2023, 24(2): 1059.
[5] CHRISTAKOS S, AJIBADE D V, DHAWAN P, et al.Vitamin D: metabolism[J]. Rheumatic Diseases Clinics of North America, 2012, 38(1): 1-11.
[6] GOLTZMAN D, HENDY G N, WHITE J H. Vitamin D and its receptor during late development[J]. Biochimica et Biophysica Acta, 2015, 1849(2): 171-180.
[7] 陈旺,孙茜,刘兆鹏.活性维生素D类药物临床研究进展[J].中国新药杂志,2019,28(23):2832-2839. CHEN Wang, SUN Qian, LIU Zhaopeng. Clinical research progress of active vitamin D drugs[J]. Chinese Journal of New Drugs, 2019, 28(23): 2832-2839.
[8] MORETTI R, MORELLI M E, CARUSO P. Vitamin D in neurological diseases: a rationale for a pathogenic impact[J]. International Journal of Molecular Sciences, 2018, 19(8): 2245.
[9] BEHL T, KAUR I, FRATILA O, et al. Exploring the potential of therapeutic agents targeted towards mitigating the events associated with amyloid-β cascade in Alzheimer’s disease[J]. International Journal of Molecular Sciences, 2020, 21(20): 7443.
[10] ONO K, WATANABE-NAKAYAMA T. Aggregation and structure of amyloid β-protein [J]. Neurochemistry International, 2021,151:105208.
[11] LAURENT C, BU?E L, BLUM D. Tau and neuroinfla-mmation:What impact for Alzheimer’s disease and Tauopathies[J]. Biomedical Journal, 2018, 41(1): 21-33.
[12] CIOFFI F, ADAM R H I, BROERSEN K. Molecular mechanisms and genetics of oxidative stress in Alzheimer’s disease[J]. Journal of Alzheimer’s Disease, 2019, 72(4): 981-1017.
[13] FAN Yongang, PANG Zhongqiu, WU Tingyao, et al. Vitamin D deficiency exacerbates Alzheimer-like pathologies by reducing antioxidant capacity [J]. Free Radical Biology and Medicine, 2020, 161:139-149.
[14] JIA Jingya, HU Jing, HUO Xiaoxu, et al. Effects of vitamin D supplementation on cognitive function and blood Aβ-related biomarkers in older adults with Alzheimer’s disease: a randomised, double-blind, placebo-controlled trial[J]. Journal of Neurology, Neurosurgery, and Psychiatry, 2019, 90(12): 1347-1352.
[15] ISRAEL L L,SUN Tao,BRAUBACH O, et al. β-Amyloid targeting nanodrug for neuron-specific delivery of nucleic acids in Alzheimer’s disease mouse models [J]. Journal of Controlled Release, 2023, 361:636-658.
[16] AR?VALO N B, CASTILLO-GODOY D P, ESPINOZA-FUENZALIDA I, et al. Association of vitamin D receptor polymorphisms with amyloid-β transporters expression and risk of mild cognitive impairment in a chilean cohort [J]. Journal Alzheimer’s Disease 2021, 82(s1):S283-S297.
[17] PATEL P, SHAH J. Role of vitamin D in amyloid clearance via LRP-1 upregulation in Alzheimer’s disease: a potential therapeutic target? [J] Journal of Chemical Neuroanatomy, 2017, 85: 36-42.
[18] GUO Y X, HE L Y, ZHANG M, et al. 1,25-Dihydroxyvitamin D3 regulates expression of LRP1 and RAGE in vitro and in vivo, enhancing Aβ1-40 brain-to-blood e?ux and peripheral uptake transport [J]. Neuroscience, 2016, 322: 28-38.
[19] BERRIDGE M J. Vitamin D and depression:cellular and regulatory mechanisms[J]. Pharmacological Reviews, 2017, 69(2): 80-92.
[20] DURSUN E, GEZEN-AK D, YILMAZER S. A novel perspective for Alzheimer’s disease:vitamin D receptor suppression by amyloid-β and preventing the amyloid-β induced alterations by vitamin D in cortical neurons[J]. Journal of Alzheimer’s Disease, 2011, 23(2): 207-219.
[21] JI Lili, TONG Lei, PENG Junbo, et al. Changes in the expression of the vitamin D receptor and LVSCC-A1C in the rat hippocampus submitted to single prolonged stress[J]. Molecular Medicine Reports, 2014, 9(4): 1165-1170.
[22] JASSIL N K,SHARMA A,BIKLE D, et al.Vitamin D binding protein and 25-hydroxy vitamin D levels:emerging clinical applications[J]. Endocrine Practice,2017, 23(5): 605-613.
[23] JEON S G,CHA M Y, KIM J I, et al.Vitamin D-binding protein-loaded PLGA nanoparticles suppress Alzheimer’s disease-related pathology in 5XFAD mice [J].Nanomedicine: Nanotechnology, Biology and Medicine, 2019, 17: 297-307.
[24] MOON M,SONG H,HONG H J, et al.Vitamin D-binding protein interacts with Aβ and suppresses Aβ-mediated pathology[J].Cell Death and Differentiation, 2013, 20(4): 630-638.
[25] SATHYA S,SHANMUGANATHAN B, BALASUBRAMA NIAM B, et al. Phytol loaded PLGA nanoparticles regulate the expression of Alzheimer’s related genes and neuronal apoptosis against amyloid-β induced toxicity in Neuro-2a cells and transgenic Caenorhabditis elegans [J]. Food and Chemical Toxicology, 2020, 136: 110962.
[26] LIU Junlin, FAN Yonggang, YANG Zhengsheng, et al. Alzheimer’s disease: from pathogenesis to therapeutic implications [J]. Frontiers in Neuroscience, 2018, 12: 632.
[27] LI Lin, LI Wenjun, ZHENG Xiangru, et al. Eriodictyol ameliorates cognitive dysfunction in APP/PS1 mice by inhibiting ferroptosis via vitamin D receptor-mediated Nrf2 activation [J]. Molecular Medicine (Cambridge, Mass.), 2022, 28(1): 11.
[28] WU Tingyao, ZHAO Lingxiao, ZHANG Yanhui, et al. Activation of vitamin D receptor inhibits Tau phosphorylation is associated with reduction of iron accumulation in APP/PS1 transgenic mice [J]. Neurochemistry International, 2022, 153: 105260.
[29] PAN Yiming, ZHANG Yalin, LIU Ning, et al. Vitamin D attenuates Alzheimer-like pathology induced by okadaic acid[J]. ACS Chemical Neuroscience, 2021, 12(8): 1343-1350.
[30] ZAULKFFALI A S, MD RAZIP N N, SYED ALWI S S, et al. Vitamins D and E stimulate the PI3K-AKT signalling pathway in insulin-resistant SK-N-SH neuronal cells[J]. Nutrients, 2019, 11(10): 2525.
[31] LIN C I, CHANG Yichen, KAO N J, et al. 1,25(OH)2D3 alleviates Aβ(25-35)-induced Tau hyperphosphorylation, excessive reactive Oxygen species, and apoptosis through interplay with glial cell line-derived neurotrophic factor signaling in SH-SY5Y cells[J]. International Journal of Molecular Sciences, 2020, 21(12): 4215.
[32] KHEIRI G, DOLATSHAHI M, RAHMANI F, et al. Role of p38/MAPKs in Alzheimer’s disease:implications for amyloid beta toxicity targeted therapy[J]. Reviews in the Neurosciences, 2018, 30(1): 9-30.
[33] SAAD EL-DIN S, RASHED L, MEDHAT E, et al. Active form of vitamin D analogue mitigates neurodegenerative changes in Alzheimer’s disease in rats by targeting Keap1/Nrf2 and MAPK-38p/ERK signaling pathways [J]. Steroids, 2020, 156: 108586.
[34] HOU Tingting, HAN Yundan, CONG Lin, et al. Apolipoprotein E facilitates amyloid-β oligomer-induced Tau phosphorylation[J]. Journal of Alzheimer’s Disease :JAD, 2020, 74(2): 521-534.
[35] GOMES L A, HIPP S A, RIJAL UPADHAYA A, et al. Aβ-induced acceleration of Alzheimer-related τ-pathology spreading and its association with prion protein[J]. Acta Neuropathologica, 2019, 138(6): 913-941.
[36] KOUTSODENDRIS N, NELSON M R, RAO A, et al. Apolipoprotein E and Alzheimer’s disease: findings, hypotheses, and potential mechanisms[J]. Annual Review of Pathology, 2022, 17: 73-99.
[37] DAFNIS I, RAFTOPOULOU C, MOUNTAKI C, et al. ApoE isoforms and carboxyl-terminal-truncated apoE4 forms affect neuronal BACE1 levels and Aβ production independently of their cholesterol efflux capacity[J]. The Biochemical Journal, 2018, 475(10):1839-1859.
[38] HUANG Y A, ZHOU Bo, WERNIG M, et al. ApoE2, ApoE3, and ApoE4 differentially stimulate APP transcription and Aβ secretion[J]. Cell, 2017, 168(3):427-441.e21.
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备注/Memo

备注/Memo:
基金项目:国家自然科学基金(82304244);首都医科大学教育教学改革研究课题(2022JYY422)。
作者简介:赵郑琪琦(2003-),女,本科,专业:卫生检验与检疫,E-mail:qq18515639285@icloud.com。
通讯作者:刘佳,女,讲师,E-mail:liujia@ccmu.edu.cn。
更新日期/Last Update: 2025-05-15