377
Views
3
CrossRef citations to date
0
Altmetric
REVIEW

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

ORCID Icon, &
Pages 3295-3323 | Received 14 Aug 2023, Accepted 02 Nov 2023, Published online: 12 Nov 2023

References

  • Academy of Cognitive Disorder of China, Writing Group of Expert Consensus on Long-term Healthcare of Cognitive Disorders in China. Chinese expert consensus on activity, behavior and cognition comprehensive management of Alzheimer’s disease. Chin J Geriatr. 2020;39(01):1–8. doi:10.3760/cma.j.issn.0254-9026.2020.01.001
  • Lynch C. World Alzheimer Report 2019: attitudes to dementia, a global survey. Alzheimer’s & Dementia. 2020;16(S10):8255. doi:10.1002/alz.038255
  • Alzheimer’s Association. 2021 Alzheimer’s disease facts and figures. Alzheimers Dement. 2021;17(3):327–406. doi:10.1002/alz.12328
  • Chinese Society of Dementia and Cognitive Impairment. Chinese expert consensus on the diagnosis and treatment of mild cognitive impairment due to Alzheimer′s disease 2021. Chin J Neurol. 2022;55(5):421–440. doi:10.3760/cma.j.cn113694-20211004-00679
  • Jia L, Du Y, Chu L, et al. Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study. Lancet Public Health. 2020;5(12):e661–e671. doi:10.1016/S2468-2667(20)30185-7
  • Wang WL, Song CS. Recent Advances in the Pathogenesis of Alzheimer′s Disease and Clinical Medication. Chin J Drug Eval. 2019;36(03):204–209. doi:10.3969/j.issn.2095-3593.2019.03.011
  • Tian JZ, Xie HG, Wang LN, et al. the Guideline Panel of the Alzheimer’s Disease Chinese(ADC).Chinese guideline for the diagnosis and treatment of Alzheimer’s disease dementia(2020). Chin J Geriatr. 2021;40(3):269–283. doi:10.3760/cma.j.issn.0254-9026.2021.03.001
  • Liu J, Wang LN, Tian JZ. Recognition of dementia in ancient China. Neurobiol Aging. 2012;33(12):2911–2948. doi:10.1016/j.neurobiolaging.2012.06.019
  • Zhang YG, Liang YQ, Li YL, et al. Talking about Alzheimer’s disease from ‘kidney deficiency phlegm stasis’ Evolution of TCM pathogenesis. Modernization Traditional Chin Med Mater Medica-World Sci Technol. 2021;23(01):159–164. doi:10.11842/wst.20200724001
  • Tian JZ, Shi J, Ni JN, et al. Sequential Therapy Based on Evolvement of Patterns: a New Model for Treatment of Alzheimer’s Disease. Chin J Integr Med. 2019;25(8):565–573. doi:10.1007/s11655-019-3066-y
  • Tian J, Shi J, Wei M, et al. Chinese herbal medicine Qinggongshoutao for the treatment of amnestic mild cognitive impairment: a 52-week randomized controlled trial. Alzheimers Dement. 2019;5:441–449. doi:10.1016/j.trci.2019.03.001.eCollection2019
  • Savaskan E, Mueller H, Hoerr R, et al. Treatment effects of Ginkgo biloba extract EGb 761 on the spectrum of behavioral and psychological symptoms of dementia: meta-analysis of randomized controlled trials. Int Psychogeriatr. 2018;30(3):285–293. doi:10.1017/S1041610217001892
  • Shi J, Ni J, Lu T, et al. Adding Chinese herbal medicine to conventional therapy brings cognitive benefits to patients with Alzheimer’s disease: a retrospective analysis. BMC Complement Altern Med. 2017;17(1):533. doi:10.1186/s12906-017-2040-5
  • Zhou XL. Research Progress of the Prevention and Treatment of Alzheimer’s Disease with Chinese Herbal Monomers and their Active Ingredients. World Latest Medi Inf. 2019;19(46):99–100.
  • Cheng XR, Zhou WX, Zhang YX. Research on the pathogenesis of Alzheimer’s disease and prevention and treatment drugs. Chin J Pharmacol Toxicol. 2017;31(12):1129–1141. doi:10.3867/j.issn.1000-3002.2017.12.001
  • Zhang YH, Yang MH, Wu DH. Research Progress of the Intervention of Monomer and Active Ingredients of Chinese Medicinal in Treatment of AD. Info Tradit Chin Med. 2019;36(03):118–122. doi:10.19656/j.cnki.1002-2406.190092
  • Ryu JC, Zimmer ER, Rosa-Neto P, et al. Consequences of Metabolic Disruption in Alzheimer’s Disease Pathology. Neurotherapeutics. 2019;16(3):600–610. doi:10.1007/s13311-019-00755-y
  • Li C, Zhao L, Zang WD. Amyloid β-protein and neural network abnormality in Alzheimer’s disease. Chin Bull Life Sci. 2021;33(07):801–809. doi:10.13376/j.cbls/2021086
  • Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med. 2016;8(6):595–608. doi:10.15252/emmm.201606210
  • Dunys J, Valverde A, Checler F. Are N- and C-terminally truncated Abeta species key pathological triggers in Alzheimer’s disease? J Biol Chem. 2018;293(40):15419–15428. doi:10.1074/jbc.R118.003999
  • Volloch V, Rits S. Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease. Med Sci. 2018;6(2). doi:10.3390/medsci6020045
  • Li L, Xia BL, Ru LQ. Curative Effectiveness of Tanshinone in the Treatment of ModeI Rats with Two Kinds of Learning and Memory Impairment. Acta Med Univ Sei Technol Huazhong. 2008;37(06):819–822. doi:10.3870/j.issn.1672-0741.2008.06.031
  • Zhuang Y, Shi B, Tian X, et al. Effects of ginsenoside Rg2 on learning and memory ability and senile plaque formation in rats with Alzheimer’s disease model. Chin J Gerontol. 2010;30(02):202–204. doi:10.3969/j.issn.1005-9202.2010.02.025
  • Lu TT, Wang YY, Huang ZT, et al. The Influence of Berberine on Learning and Memory Ability and Amyloid Expression in APP/PS1 Transgenic Mice. Chin J Integr Med Cerebrovasc Dis. 2019;17(08):1155–1161.
  • Niu K, Chen Y, Xiao YY, et al. Effect of β-asarone on the deposition of β-amyloid in the brain of AD mice. J Hefei Univ Technol, Nat Sci. 2022;45(04):561–564. doi:10.3969/j.issn.1003-5060.2022.04.022
  • Xiao F, Luo HM, Li XG, et al. Inhibition of γ-schisandrin on the production of amyloid β-protein from M146L cells. Chin J New Drugs. 2005;1(3):290–292. doi:10.3321/j.issn:1003-3734.2005.03.010
  • Li Z, Liu XC, Li R, et al. Reduction of Aβ Generation by Schisandrin B through Restraining Beta-Secretase 1 Transcription and Translation. Med Sci Monit. 2018;24:1219–1224. doi:10.12659/msm.905127
  • Chen Q, Gao CX, Ge LH. The Effect of Senegenin on Neuromorphopathological Changes of AD Rats with β-Amyloid1-40 Injection into Right. Nucleus Basalis Acta Laser Biol Sin. 2006;2006(3):294–298. doi:10.3389/fphar.2022.937333
  • Webster B, Hansen L, Adame A, et al. Astroglial activation of extracellular-regulated kinase in early stages of Alzheimer disease. J Neuropathol Exp Neurol. 2006;65(2):142–151. doi:10.1097/01.jnen.0000199599.63204.6f
  • Qi H, Prabakaran S, Cantrelle FX, et al. Characterization of Neuronal Tau Protein as a Target of Extracellular Signal-regulated Kinase. J Biol Chem. 2016;291(14):7742–7753. doi:10.1074/jbc.M115.700914
  • Li SX, Han YS, Ji XY, et al. The Influence of Curcumin on the Expression of ERK Protein in Hippocampal Neurons Induced by Aβ in Rats with Alzheimer’s. Disease Acta Chin Med Pharmacol. 2014;42(02):21–23. doi:10.19664/j.cnki.1002-2392.2014.02.008
  • Sun T, Zhang DS, Jing YS. Therapeutic effect of curcumin on Alzheimer’s disease and its mechanism. Chin J Pharmacol Toxicol. 2021;35(09):641.
  • Ma YX, Jiao JL, Liu CY, et al. Effect of rhizoma acori graminei on the secondary structure of amyloid beta-protein 25-35. Chin J Pathophysiol. 2007;2:352–355. doi:10.3321/j.issn:1000-4718.2007.02.033
  • Huang X, Liu G, Guo J, et al. The PI3K/AKT pathway in obesity and type 2 diabetes. Int J Biol Sci. 2018;14(11):1483–1496. doi:10.7150/ijbs.27173
  • Xie Y, Shi X, Sheng K, et al. PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia(Review). Mol Med Rep. 2019;19(2):783–791. doi:10.3892/mmr.2018.9713
  • Gabbouj S, Ryhanen S, Marttinen M, et al. Altered Insulin Signaling in Alzheimer’s Disease Brain - Special Emphasis on PI3K-Akt Pathway. Front Neurosci. 2019;13:629. doi:10.3389/fnins.2019.00629
  • Zhang B, Wang Y, Li H, et al. Neuroprotective effects of salidroside through PI3K/Akt pathway activation in Alzheimer’s disease models. Drug Des Devel Ther. 2016;10:1335–1343. doi:10.2147/DDDT.S99958
  • Wang H, Li Q, Sun S, et al. Neuroprotective Effects of Salidroside in a Mouse Model of Alzheimer’s Disease. Cell Mol Neurobiol. 2020;40(7):1133–1142. doi:10.1007/s10571-020-00801-w
  • Guo B, Zhang W, Xu S, et al. GSK-3beta mediates dexamethasone-induced pancreatic beta cell apoptosis. Life Sci. 2016;144:1–7. doi:10.1016/j.lfs.2015.11.017
  • Luo CC, Yuan CY, Chen QF. GOLPH3 regulates proliferation and apoptosis of endometrial carcinoma cells through PI3K/AKT/GSK3βsignal. J Int Oncol. 2020;47(02):65–69. doi:10.3760/cma.j.issn.1673-422X.2020.02.001
  • Sun XY, J LL, Dong QX, et al. Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer’s disease. J Neuroinflammation. 2021;18(1):131. doi:10.1186/s12974-021-02182-3
  • Ma GX, Ding QP, Deng HH, et al. Effect of astragalus polysaccharide and mechanism on Alzheimer’s disease rats. Stroke nerv dis. 2017;24(04):323–327. doi:10.3969/j.issn.1007-0478.2017.04.011
  • Du J, Murphy RM. Characterization of the interaction of beta-amyloid with transthyretin monomers and tetramers. Biochemistry. 2010;49(38):8276–8289. doi:10.1021/bi101280t
  • Lin M, Wang M, Gao SQ, et al. Effect of resveratrol on cognitive function and the expression of Aβ1-40 and Aβ1-42 in cerebral cortex of model mice with Alzheimer’s disease. J Mod Med Health. 2017;33(16):2425–2427. doi:10.3969/j.issn.1009-5519.2017.16.006
  • Santos LM, Rodrigues D, Alemi M, et al. Resveratrol administration increases Transthyretin protein levels ameliorating AD features- importance of transthyretin tetrameric stability. Mol Med. 2016;22:597–607. doi:10.2119/molmed.2016.00124
  • Duckworth WC, Bennett RG, Hamel FG. Insulin degradation: progress and potential. Endocr Rev. 1998;19(5):608–624. doi:10.1210/edrv.19.5.0349
  • Son SM, Cha MY, Choi H, et al. Insulin-degrading enzyme secretion from astrocytes is mediated by an autophagy-based unconventional secretory pathway in Alzheimer disease. Autophagy. 2016;12(5):784–800. doi:10.1080/15548627.2016.1159375
  • Vekrellis K, Ye Z, Qiu WQ, et al. Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme. J Neurosci. 2000;20(5):1657–1665. doi:10.1523/JNEUROSCI.20-05-01657.2000
  • Jha NK, Jha SK, Kumar D, et al. Impact of Insulin Degrading Enzyme and Neprilysin in Alzheimer’s Disease Biology: characterization of Putative Cognates for Therapeutic Applications. J Alzheimers Dis. 2015;48(4):891–917. doi:10.3233/JAD-150379
  • Lei DL, Li MB, Xiong K, et al. Triptolide inhibits the Aβ deposition and senile plaques formation in the hippocampus of APP/PS1 double transgenic mice. Acta Anat Sin. 2009;40(03):369–373. doi:10.3969/j.issn.0529-1356.2009.03.005
  • Cheng S, Leblanc KJ, Li L. Triptolide preserves cognitive function and reduces neuropathology in a mouse model of Alzheimer’s disease. PLoS One. 2014;9(9):e108845. doi:10.1371/journal.pone.0108845
  • Wang Q, Xiao B, Cui S, et al. Triptolide treatment reduces Alzheimer’s disease (AD)-like pathology through inhibition of BACE1 in a transgenic mouse model of AD. Dis Model Mech. 2014;7(12):1385–1395. doi:10.1242/dmm.018218
  • Huang JL, Feng YQ, Bai LR, et al. Fraction n-Butanol of Radix Notoginseng Protects PC12 Cells from Abeta(25-35)-Induced Cytotoxicity and Alleviates Cognitive Deficits in SAMP8 Mice by Attenuating Oxidative Stress and Abeta Accumulation. Evid Based Complement Alternat Med. 2017;2017:8469754. doi:10.1155/2017/8469754
  • Jin K, Peel AL, Mao XO, et al. Increased hippocampal neurogenesis in Alzheimer’s disease. Proc Natl Acad Sci U S A. 2004;101(1):343–347. doi:10.1073/pnas.2634794100
  • Liu CY, Zhang PX, Rong GY, et al. Effects of tetramethylpyrazine on the expression of APP and NEP in the brain of rats with Alzheimer’s disease (AD) model. Heiilongjiang Medi Pharm. 2016;39(03):8–9. doi:10.3969/j.issn.1008-0104.2016.03.004
  • Liu SZ, Cheng W, Shao JW, et al. Notoginseng Saponin Rg1 Prevents Cognitive Impairment through Modulating APP Processing in Abeta(1-42)-injected Rats. Curr Med Sci. 2019;39(2):196–203. doi:10.1007/s11596-019-2019-1
  • Moreno-Jimenez EP, Flor-Garcia M, Terreros-Roncal J, et al. Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nat Med. 2019;25(4):554–560. doi:10.1038/s41591-019-0375-9
  • Erlandsson A, Lin CH, Yu F, et al. Immunosuppression promotes endogenous neural stem and progenitor cell migration and tissue regeneration after ischemic injury. Exp Neurol. 2011;230(1):48–57. doi:10.1016/j.expneurol.2010.05.018
  • Kolb B, Morshead C, Gonzalez C, et al. Growth factor-stimulated generation of new cortical tissue and functional recovery after stroke damage to the motor cortex of rats. J Cereb Blood Flow Metab. 2007;27(5):983–997. doi:10.1038/sj.jcbfm.9600402
  • Jin K, Galvan V, Xie L, et al. Enhanced neurogenesis in Alzheimer’s disease transgenic (PDGF-APPSw, Ind) mice. Proc Natl Acad Sci U S A. 2004;101(36):13363–13367. doi:10.1073/pnas.0403678101
  • Niidome T, Taniuchi N, Akaike A, et al. Differential regulation of neurogenesis in two neurogenic regions of APPswe/PS1dE9 transgenic mice. Neuroreport. 2008;19(14):1361–1364. doi:10.1097/WNR.0b013e32830e6dd6
  • Rodriguez JJ, Jones VC, Tabuchi M, et al. Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer’s disease. PLoS One. 2008;3(8):e2935. doi:10.1371/journal.pone.0002935
  • Cheung WM, Hui WS, Chu PW, et al. Ganoderma extract activates MAP kinases and induces the neuronal differentiation of rat pheochromocytoma PC12 cells. FEBS Lett. 2000;486(3):291–296. doi:10.1016/s0014-5793(00)02317-6
  • Chu QP, Wang LE, Cui XY, et al. Extract of Ganoderma lucidum potentiates pentobarbital-induced sleep via a GABAergic mechanism. Pharmacol Biochem Behav. 2007;86(4):693–698. doi:10.1016/j.pbb.2007.02.015
  • Matsuzaki H, Shimizu Y, Iwata N, et al. Antidepressant-like effects of a water-soluble extract from the culture medium of Ganoderma lucidum mycelia in rats. BMC Complement Altern Med. 2013;13:370. doi:10.1186/1472-6882-13-370
  • Qin C, Wu SQ, Chen BS, et al. Pathological Changes in APP/PS-1 Transgenic Mouse Models of Alzheimer’s Disease Treated with Ganoderma lucidum Preparation. Acta Acad Med Sin. 2017;39(4):552–561. doi:10.3881/j.issn.1000-503X.2017.04.015
  • Huang S, Mao J, Ding K, et al. Polysaccharides from Ganoderma lucidum Promote Cognitive Function and Neural Progenitor Proliferation in Mouse Model of Alzheimer’s Disease. Stem Cell Reports. 2017;8(1):84–94. doi:10.1016/j.stemcr.2016.12.007
  • Wang Q, Zhang L, Yuan X, et al. The Relationship between the Bcl-2/Bax Proteins and the Mitochondria-Mediated Apoptosis Pathway in the Differentiation of Adipose-Derived Stromal Cells into Neurons. PLoS One. 2016;11(10):e163327. doi:10.1371/journal.pone.0163327
  • Wang C, Yao B, Xu M, et al. RIP1 upregulation promoted tumor progression by activating AKT/Bcl-2/BAX signaling and predicted poor postsurgical prognosis in HCC. Tumour Biol. 2016;37(11):15305–15313. doi:10.1007/s13277-016-5342-1
  • Saito A, Suga K, Ono-Nakagawa R, et al. Time lapse imaging analysis of the effect of ER stress modulators on apoptotic cell assessed by caspase3/7 activation in NG108-15 cells. Data Brief. 2016;6:20–27. doi:10.1016/j.dib.2015.11.030
  • Liu ZZ, Fu X, Chen G, et al. Combined effects and mechanism of lactate dehydrogenase A gene knockout and mitomycin C on prostate cancer cell apoptosis. Chin J Biomed Eng. 2016;22(3):206–209. doi:10.3760/cma.j.issn.1674-1927.2016.03.006
  • Mitupatum T, Aree K, Kittisenachai S, et al. mRNA Expression of Bax, Bcl-2, p53, Cathepsin B, Caspase-3 and Caspase-9 in the HepG2 Cell Line Following Induction by a Novel Monoclonal Ab Hep88 mAb: cross-Talk for Paraptosis and Apoptosis. Asian Pac J Cancer Prev. 2016;17(2):703–712. doi:10.7314/apjcp.2016.17.2.703
  • Liu C, Wang Y, Wang JY, et al. Expression of Bax on beta-amyloid (Aβ) -induced PC12 cell by Anemarrhena total saponins. Chin J Gerontol. 2014;34(18):5163–5165. doi:10.3969/j.issn.1005-9202.2014.18.68
  • Yin G, Gong DK, Liu BH, et al. Effects of Cistanche polysaccharide on learning and memory ability and expression of Bcl-2 and caspase-3 in hippocampal neurons of rats with Alzheimer’s disease. Lishizhen Med Mater Med Res. 2013;24(05):1091–1092. doi:10.3969/j.issn.1008-0805.2013.05.027
  • Luo L, Wang XW, Shi KR, et al. Preliminary study on the pathomorphology of the Glycosides of Cistanche Herba on the hippocampal CA1 area of experimental AD rats induced by β-amyloid. J North Sichuan Med Coll. 2020;35(06):947–951. doi:10.3969/j.issn.1005-3697.2020.06.02
  • Xiao F, Li XG, Gao Q, et al. The inhibition of amyloid β-protein production in M146L cell by Kadsura heteroclita polysaccharide. Chin J Gerontol. 2009;29(19):2458–2460. doi:10.3969/j.issn.1005-9202.2009.19.017
  • Xue JC. Effects of wogonoside on the nerves of APP/PS1 double transgenic mice neuroprotection and its mechanism. Guang zhou: Guangzhou University of Chinese Medicine; 2021. doi:10.27044/d.cnki.ggzzu.2021.001040
  • Hu XY, Sun XQ, Li ZP. Protective effect of phillyrin on HT22 cells and APP/PS1 mice induced by L-glutamate. Chin J Gerontol. 2022;42(07):1710–1714. doi:10.3969/j.issn.1005-9202.2022.07.051
  • Tayler H, Miners JS, Guzel O, et al. Mediators of cerebral hypoperfusion and blood-brain barrier leakiness in Alzheimer’s disease, vascular dementia and mixed dementia. Brain Pathol. 2021;31(4):e12935. doi:10.1111/bpa.12935
  • He Y, Ruganzu JB, Zheng Q, et al. Silencing of LRP1 Exacerbates Inflammatory Response Via TLR4/NF-kappaB/MAPKs Signaling Pathways in APP/PS1 Transgenic Mice. Mol Neurobiol. 2020;57(9):3727–3743. doi:10.1007/s12035-020-01982-7
  • Aurelie N. LRP1 plays a major role in the amyloid-β clearance in microglia. Mol Neurodegener. 2013;8:S1. doi:10.1186/1750-1326-8-S1-P33
  • Pascale CL, Miller MC, Chiu C, et al. Amyloid-beta transporter expression at the blood-CSF barrier is age-dependent. Fluids Barriers CNS. 2011;8:21. doi:10.1186/2045-8118-8-21
  • Zhao XS. Effects and Mechanism of Ox-LDL on Neural Cells Apoptosis Mediated by PCSK9/LRP1. Hu Nan: University of South China; 2016.
  • Chen HD. The Mechanism of the Aβ Clearance by Baicailin Through Blood Brain Barrier Pathwayin Alzheimer’s Disease Mouse. Guang zhou: Guang zhou university of chinese medicine; 2021. doi:10.27044/d.cnki.ggzzu.2021.001038
  • Tang G, Tang X, Mendu V, et al. The art of microRNA: various strategies leading to gene silencing via an ancient pathway. Biochim Biophys Acta. 2008;1779(11):655–662. doi:10.1016/j.bbagrm.2008.06.006
  • Mcgeer PL, Mcgeer EG. NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies. Neurobiol Aging. 2007;28(5):639–647. doi:10.1016/j.neurobiolaging.2006.03.013
  • Lin Y, Yao YJ, Liang XC, et al. Osthole suppresses BACE-1 expression by up-regulating miR-9 in Alzheimer’s disease. Chin Pharmacol Bull. 2019;35(04):524–529. doi:10.3969/j.issn.1001-1978.2019.04.016
  • Canet G, Chevallier N, Zussy C, et al. Central Role of Glucocorticoid Receptors in Alzheimer’s Disease and Depression. Front Neurosci. 2018;12:739. doi:10.3389/fnins.2018.00739
  • Doody RS, Raman R, Farlow M, et al. A Phase 3 trial of semagacestat for treatment of Alzheimer’s disease. N Engl J Med. 2013;369(4):341–350. doi:10.1056/NEJMoa1210951
  • Salloway S, Sperling R, Fox NC, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014;370(4):322–333. doi:10.1056/NEJMoa1304839
  • Doody RS, Thomas RG, Farlow M, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014;370(4):311–321. doi:10.1056/NEJMoa1312889
  • Xia ZY, Zhao H, Pan LX, et al. Research progress on the role of Tau protein in Alzheimer’s disease. Neural Inj Functional Reconstruction. 2019;14(09):450–453. doi:10.16780/j.cnki.sjssgncj.2019.09.006
  • Dai XY, Zhang LY, Ren J, et al. Effect of glutamate receptor antagonist on learning-memory impairment and protein Tau hyperphosphorylation in neonatal rats after fetal distress. Chin Med. 2016;11(11):1718–1723. doi:10.3760/cma.j.issn.1673-4777.2016.11.032
  • Zhu ZP, Zhu H. Research progress in imaging agents targeting Aβ and Tau protein in Alzheimer′s disease. Chin J Nucl Med Mol Imaging. 2018;38(4):291–294. doi:10.3760/cma.j.issn.2095-2848.2018.04.018
  • Stefanoska K, Gajwani M, Tan A, et al. Alzheimer’s disease: ablating single master site abolishes tau hyperphosphorylation. Sci Adv. 2022;8(27):l8809. doi:10.1126/sciadv.abl8809
  • Xu KL, Chen Q, Liu W, et al. Effect of senegenin on tau protein phosphorylation at Ser396 site in neurons of AD rats induced by Aβ1-40. Chin J Pathophysiol. 2012;28(09):1605–1609. doi:10.3969/j.issn.1000-4718.2012.09.012
  • Ye J, Yin Y, Liu H, et al. Tau inhibits PKA by nuclear proteasome-dependent PKAR2alpha elevation with suppressed CREB/GluA1 phosphorylation. Aging Cell. 2020;19(1):e13055. doi:10.1111/acel.13055
  • Hu H, Liao ZD. Phosphorylation and dephosphorylation of tau protein in Alzheimer’s disease. Guang X Med J. 2010;32(05):602–605. doi:10.3969/j.issn.0253-4304.2010.05.043
  • Trushina NI, Bakota L, Mulkidjanian AY, et al. The Evolution of Tau Phosphorylation and Interactions. Front Aging Neurosci. 2019;11:256. doi:10.3389/fnagi.2019.00256
  • Li X, Zhang X, Zhang ZY, et al. The effects of Gensenoside Rg1 on the expressions of P-Tau and PKA on the brain slices of AD model rats. Chin J Gerontol. 2009;29(19):2468–2470. doi:10.3969/j.issn.1005-9202.2009.19.021
  • Li MZ, Wu WH, Wu ZP, et al. Panax Notoginseng Saponins Rg1 Improves Spatial Cognitive Ability and Decreases Phosphorylation Level of Tau Protein in Alzheimer’s Disease Rat Model. Acta Med Univ Sci Technol Huazhong. 2017;46(03):248–252. doi:10.3870/j.issn.1672-0741.2017.03.002
  • Sun DM. Therapeutic effects of curcumin in mice with Alzheimer’s disease. Chin J Gerontol. 2019;39(18):4577–4580. doi:10.3969/j.issn.1005-9202.2019.18.063
  • Wang H, Sui H, Zheng Y, et al. Curcumin-primed exosomes potently ameliorate cognitive function in AD mice by inhibiting hyperphosphorylation of the Tau protein through the AKT/GSK-3beta pathway. Nanoscale. 2019;11(15):7481–7496. doi:10.1039/c9nr01255a
  • Metaxas A, Kempf SJ. Neurofibrillary tangles in Alzheimer’s disease: elucidation of the molecular mechanism by immunohistochemistry and tau protein phospho-proteomics. Neural Regen Res. 2016;11(10):1579–1581. doi:10.4103/1673-5374.193234
  • Iqbal K, Gong CX, Liu F. Microtubule-associated protein tau as a therapeutic target in Alzheimer’s disease. Expert Opin Ther Targets. 2014;18(3):307–318. doi:10.1517/14728222.2014.870156
  • Yan HM, Du XB, Zhang JJ. Effect of Radix Angelica Sinensis on Alzheimer’s disease-like lesions and cognitive function in rats with chronic cerebral hypoperfusion. Chin J Geriatr Heart, Brain Vessel Dis. 2017;19(07):699–703. doi:10.3969/j.issn.1009-0126.2017.07.007
  • Chen H, Lombes M, Le Menuet D. Glucocorticoid receptor represses brain-derived neurotrophic factor expression in neuron-like cells. Mol Brain. 2017;10(1):12. doi:10.1186/s13041-017-0295-x
  • Riise J, Plath N, Pakkenberg B, et al. Aberrant Wnt signaling pathway in medial temporal lobe structures of Alzheimer’s disease. J Neural Transm. 2015;122(9):1303–1318. doi:10.1007/s00702-015-1375-7
  • Fiorentini A, Rosi MC, Grossi C, et al. Lithium improves hippocampal neurogenesis, neuropathology and cognitive functions in APP mutant mice. PLoS One. 2010;5(12):e14382. doi:10.1371/journal.pone.0014382
  • Kim SE, Huang H, Zhao M, et al. Wnt stabilization of beta-catenin reveals principles for morphogen receptor-scaffold assemblies. Science. 2013;340(6134):867–870. doi:10.1126/science.1232389
  • Willert K, Jones KA. Wnt signaling: is the party in the nucleus? Genes Dev. 2006;20(11):1394–1404. doi:10.1101/gad.1424006
  • Clevers H, Nusse R. Wnt/beta-catenin signaling and disease. Cell. 2012;149(6):1192–1205. doi:10.1016/j.cell.2012.05.012
  • Huo JT, Zhang XQ, Yan J, et al. Activation of Wnt signaling pathway by tetramethylpyrazine improves brain tissue inflammation in rats with Alzheimer’s disease. Zhejiang Clin Med J. 2015;2015(8):1262–1264.
  • Yao HT, Ma JL, Zhang XB, et al. Effect of Cornus officinalis polysaccharide on tau protein in Alzheimer’s disease model rats. Chin J Gerontol. 2013;33(12):2838–2841. doi:10.3969/j.issn.1005-9202.2013.12.047
  • Su YN, Yao HT, Zhang XB, et al. Effects of Cornus officinale polysaccharide on glycogen synthase kinase-3β and phosphorylated-tau protein in the hippocampus of rats with an Alzheimer’s disease model. Chin J Gerontol. 2017;37(12):2885–2887. doi:10.3969/j.issn.1005-9202.2017.12.010
  • Li H, Liu C, Li N, et al. Improvement of acidic polysaccharose of Schisandra Chinensis on learning and memory functions of Alzheimer’s disease model mice. J Jilin Univ, Med Ed. 2017;43(06):1115–1120. doi:10.13481/j.1671-587x.20170609
  • Ni YN, Wang MY, Kong L, et al. Effect of osthole on tau hyperphosphorylation and PI3K/Akt/Gsk3β signaling pathway in the brain of AD mice. Chin New Drugs J. 2019;28(23):2865–2871. doi:10.3969/j.issn.1003-3734.2019.23.013
  • Lee MS, Kwon YT, Li M, et al. Neurotoxicity induces cleavage of p35 to p25 by calpain. Nature. 2000;405(6784):360–364. doi:10.1038/35012636
  • Patrick GN, Zukerberg L, Nikolic M, et al. Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature. 1999;402(6762):615–622. doi:10.1038/45159
  • Alvarez A, Toro R, Caceres A, et al. Inhibition of tau phosphorylating protein kinase cdk5 prevents beta-amyloid-induced neuronal death. FEBS Lett. 1999;459(3):421–426. doi:10.1016/s0014-5793(99)01279-x
  • Shi LL, Yang WN, Chen XL, et al. The protective effects of tanshinone IIA on neurotoxicity induced by beta-amyloid protein through calpain and the p35/Cdk5 pathway in primary cortical neurons. Neurochem Int. 2012;61(2):227–235. doi:10.1016/j.neuint.2012.04.019
  • Lin L, Jadoon SS, Liu SZ, et al. Tanshinone IIA Ameliorates Spatial Learning and Memory Deficits by Inhibiting the Activity of ERK and GSK-3beta. J Geriatr Psychiatry Neurol. 2019;32(3):152–163. doi:10.1177/0891988719837373
  • Gong CX, Liu F, Grundke-Iqbal I, et al. Post-translational modifications of tau protein in Alzheimer’s disease. J Neural Transm. 2005;112(6):813–838. doi:10.1007/s00702-004-0221-0
  • Sanchez-Mut JV, Aso E, Heyn H, et al. Promoter hypermethylation of the phosphatase DUSP22 mediates PKA-dependent TAU phosphorylation and CREB activation in Alzheimer’s disease. Hippocampus. 2014;24(4):363–368. doi:10.1002/hipo.22245
  • Szegeczki V, Horvath G, Perenyi H, et al. Alzheimer’s Disease Mouse as a Model of Testis Degeneration. Int J Mol Sci. 2020;21(16). doi:10.3390/ijms21165726
  • Vogelsberg-Ragaglia V, Schuck T, Trojanowski JQ, et al. PP2A mRNA expression is quantitatively decreased in Alzheimer’s disease hippocampus. Exp Neurol. 2001;168(2):402–412. doi:10.1006/exnr.2001.7630
  • Sontag JM, Sontag E. Protein phosphatase 2A dysfunction in Alzheimer’s disease. Front Mol Neurosci. 2014;7:548.
  • Chen Q, et al. Banqiao Codonopsis pilosula improves cognitive dysfunction in AD model rats by PP2A signaling pathway. Chin Pharmacol Bull. 2019;35:1232–1239. doi:10.3969/j.issn.1001-1978.2019.09.010
  • Xie WZ. Trillium tschonoskii maxim improves cognitive dysfunction in Alzheimer’s disease induced by okadaic acid in rats and its possible mechanism. Chin Pharmacol Bull. 2018;34:1268–1275. doi:10.3969/j.issn.1001-1978.2018.09.017
  • Ma D, et al. Cornel iridoid glycoside suppresses tau hyperphosphorylation and aggregation in a mouse model of tauopathy through increasing activity of PP2A. Curr Alzheimer Res. 2019;16:1316–1331. doi:10.2174/1567205017666200103113158
  • Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2010;22(2):124–131. doi:10.1016/j.ceb.2009.11.014
  • Nixon RA. The role of autophagy in neurodegenerative disease. Nat Med. 2013;19(8):983–997. doi:10.1038/nm.3232
  • Menzies FM, Fleming A, Rubinsztein DC. Compromised autophagy and neurodegenerative diseases. Nat Rev Neurosci. 2015;16(6):345–357. doi:10.1038/nrn3961
  • Menzies FM, Fleming A, Caricasole A, et al. Autophagy and Neurodegeneration: pathogenic Mechanisms and Therapeutic Opportunities. Neuron. 2017;93(5):1015–1034. doi:10.1016/j.neuron.2017.01.022
  • Kumar H, Kim IS, More SV, et al. Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases. Nat Prod Rep. 2014;31(1):109–139. doi:10.1039/c3np70065h
  • Mbaveng AT, Kuete V, Efferth T. Potential of Central, Eastern and Western Africa Medicinal Plants for Cancer Therapy: spotlight on Resistant Cells and Molecular Targets. Front Pharmacol. 2017;8:343. doi:10.3389/fphar.2017.00343
  • Pickford F, Masliah E, Britschgi M, et al. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J Clin Invest. 2008;118(6):2190–2199. doi:10.1172/JCI33585
  • Ni HM, Chao X, Yang H, et al. Dual Roles of Mammalian Target of Rapamycin in Regulating Liver Injury and Tumorigenesis in Autophagy-Defective Mouse Liver. Hepatology. 2019;70(6):2142–2155. doi:10.1002/hep.30770
  • Ni HM, Mcgill MR, Chao X, et al. Removal of Acetaminophen protein adducts by autophagy protects against Acetaminophen-induced liver injury in mice. J Hepatol. 2016;65(2):354–362. doi:10.1016/j.jhep.2016.04.025
  • Nilsson P, Loganathan K, Sekiguchi M, et al. Abeta secretion and plaque formation depend on autophagy. Cell Rep. 2013;5(1):61–69. doi:10.1016/j.celrep.2013.08.042
  • Nilsson P, Sekiguchi M, Akagi T, et al. Autophagy-related protein 7 deficiency in amyloid beta (Abeta) precursor protein transgenic mice decreases Abeta in the multivesicular bodies and induces Abeta accumulation in the Golgi. Am J Pathol. 2015;185(2):305–313. doi:10.1016/j.ajpath.2014.10.011
  • Uddin MS, Stachowiak A, Mamun AA, et al. Autophagy and Alzheimer’s Disease: from Molecular Mechanisms to Therapeutic Implications. Front Aging Neurosci. 2018;10:4. doi:10.3389/fnagi.2018.00004
  • Mizushima N, Yoshimori T. How to interpret LC3 immunoblotting. Autophagy. 2007;3(6):542–545. doi:10.4161/auto.4600
  • Ohashi Y, Tremel S, Williams RL. VPS34 complexes from a structural perspective. J Lipid Res. 2019;60(2):229–241. doi:10.1194/jlr.R089490
  • Jaeger PA, Wyss-Coray T. Beclin 1 complex in autophagy and Alzheimer disease. Arch Neurol. 2010;67(10):1181–1184. doi:10.1001/archneurol.2010.258
  • Zhou KY, Hu Y, Yang M, et al. Baicalin improves cognitive function by delaying senescence and regulating autophagy activity in Tau transgenic mice. Chin New Drugs J. 2019;28(01):65–72.
  • Settembre C, Di malta C, Polito VA, et al. TFEB links autophagy to lysosomal biogenesis. Science. 2011;332(6036):1429–1433. doi:10.1126/science.1204592
  • Sardiello M, Palmieri M, Di Ronza A, et al. A gene network regulating lysosomal biogenesis and function. Science. 2009;325(5939):473–477. doi:10.1126/science.1174447
  • Martina JA, Chen Y, Gucek M, et al. MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB. Autophagy. 2012;8(6):903–914. doi:10.4161/auto.19653
  • Liu J, Zhang Y, Liu A, et al. Distinct Dasatinib-Induced Mechanisms of Apoptotic Response and Exosome Release in Imatinib-Resistant Human Chronic Myeloid Leukemia Cells. Int J Mol Sci. 2016;17(4):531. doi:10.3390/ijms17040531
  • Polito VA, Li H, Martini-Stoica H, et al. Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB. EMBO Mol Med. 2014;6(9):1142–1160. doi:10.15252/emmm.201303671
  • Martini-Stoica H, Xu Y, Ballabio A, et al. The Autophagy-Lysosomal Pathway in Neurodegeneration: a TFEB Perspective. Trends Neurosci. 2016;39(4):221–234. doi:10.1016/j.tins.2016.02.002
  • Yang C, Su C, Iyaswamy A, et al. Celastrol enhances transcription factor EB (TFEB)-mediated autophagy and mitigates Tau pathology: implications for Alzheimer’s disease therapy. Acta Pharm Sin B. 2022;12(4):1707–1722. doi:10.1016/j.apsb.2022.01.017
  • Ferrari A, Hoerndli F, Baechi T, et al. beta-Amyloid induces paired helical filament-like tau filaments in tissue culture. J Biol Chem. 2003;278(41):40162–40168. doi:10.1074/jbc.M308243200
  • Götz J, Chen F, van Dorpe J, et al. Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science. 2001;293(5534):1491–1495. doi:10.1126/science.1062097
  • Bolmont T, Clavaguera F, Meyer-Luehmann M, et al. Induction of tau pathology by intracerebral infusion of amyloid-beta -containing brain extract and by amyloid-beta deposition in APP x Tau transgenic mice. Am J Pathol. 2007;171(6):2012–2020. doi:10.2353/ajpath.2007.070403
  • Desikan RS, McEvoy LK, Thompson WK, et al. Amyloid-beta associated volume loss occurs only in the presence of phospho-tau. Ann Neurol. 2011;70(4):657–661. doi:10.1002/ana.22509
  • Fortea J, Vilaplana E, Alcolea D, et al. Cerebrospinal fluid beta-amyloid and phospho-tau biomarker interactions affecting brain structure in preclinical Alzheimer disease. Ann Neurol. 2014;76(2):223–230. doi:10.1002/ana.24186
  • Busche MA, Hyman BT. Synergy between amyloid-beta and tau in Alzheimer’s disease. Nat Neurosci. 2020;23(10):1183–1193. doi:10.1038/s41593-020-0687-6
  • Hanseeuw BJ, Betensky RA, Schultz AP, et al. Fluorodeoxyglucose metabolism associated with tau-amyloid interaction predicts memory decline. Ann Neurol. 2017;81(4):583–596. doi:10.1002/ana.24910
  • Perez-Nievas BG, Stein TD, Tai HC, et al. Dissecting phenotypic traits linked to human resilience to Alzheimer’s pathology. Brain. 2013;136(Pt 8):2510–2526. doi:10.1093/brain/awt171
  • Prinz M, Jung S, Priller J. Microglia Biology: one Century of Evolving Concepts. Cell. 2019;179(2):292–311. doi:10.1016/j.cell.2019.08.053
  • Yoshiyama Y, Higuchi M, Zhang B, et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron. 2007;53(3):337–351. doi:10.1016/j.neuron.2007.01.010
  • Zhang XL, Zeng JY, Chen X, et al. Comparison and Interpretation of Chinese and British Guidelines about Therapeutic Drugs for Alzheimer’s Disease. Chin Gen Pract. 2021;24(12):1454–1458. doi:10.12114/j.issn.1007-9572.2021.00.121
  • Zhang HB, Xu Y, Chen B, et al. A meta-analysis of the prevalence of Alzheimer’s disease. Chin J Gerontol. 2018;38(9):2157–2162. doi:10.3969/j.issn.1005-9202.2018.09.045
  • Swanson CJ, Zhang Y, Dhadda S, et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody. Alzheimers Res Ther. 2021;13(1):80. doi:10.1186/s13195-021-00813-8
  • Wischik CM, Edwards PC, Lai RY, et al. Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines. Proceed Natl Acad Sci U S A. 1996;93(20):11213–11218. doi:10.1073/pnas.93.20.11213
  • Gauthier S, Feldman HH, Schneider LS, et al. Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer′s disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet. 2016;388(10062):2873–2884. doi:10.1016/S0140-6736(16)31275-2
  • Novak P, Zilka N, Zilkova M, et al. AADvac1, an active immunotherapy for Alzheimer′s disease and non Alzheimer tauopathies: an overview of preclinical and clinical development. J Prev Alzheimers Dis. 2018;6(1):1–7. doi:10.14283/jpad.2018.45