Research progress on model of Alzheimer's disease in vitro#br#

doi:10.12092/j.issn.1009-2501.2020.10.014

Abstract

Abstract: Alzheimer's disease (AD) is a neurodegenerative disease that seriously affects the quality of life of patients. Hitherto, the specific pathogenesis of AD has not been clarified and the only 5 anti-AD drugs approved for marketing also have some problems such as obvious side effects and limited efficacy. The ideal disease model is an important tool to explore the etiology and develop new drugs. This paper focuses on the traditional "induced" AD model in vitro. The modeling agents, basic principle, main characteristics and application examples are described, and the research progress of new AD models in vitro in recent years are summarized, in order to provide reference and guidance for researchers to study AD.

Key words: Alzheimer's disease, model in vitro, modeling agent

CLC Number:

R741

LI Hongxing, ZHANG Xinyue, WU Ningzi, GU Lili, LU Jiaqi, ZHANG Lingxi, LI Qin. Research progress on model of Alzheimer's disease in vitro#br#[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(10): 1178-1187.

References ［62］

［1］	王欢, 杨解人, 张俊秀, 等. 芝麻素对阿尔茨海默病大鼠学习记忆及海马谷氨酸表达的影响［J］. 中国临床药理学与治疗学, 2017, 22(5): 507511.
［2］	Wang P, Wang ZY. Metal ions influx is a double edged sword for the pathogenesis of Alzheimer's disease ［J］. Ageing Res Rev, 2017, 35: 265290.
［3］	Atri A. Current and future treatments in Alzheimer's disease ［J］. Semin Neurol, 2019, 39(2): 227240.
［4］	Liu XQ, Deng YX, Dai Z, et al. Sodium tanshinone IIA sulfonate protects against Aβ142induced cellular toxicity by modulating Aβdegrading enzymes in HT22 cells ［J］. Int J Biol Macromol, 2020, 151: 4755.
［5］	Wang HW, Pasternak JF, Kuo H, et al. Soluble oligomers of beta amyloid (142) inhibit longterm potentiation but not longterm depression in rat dentate gyrus ［J］. Brain Res, 2002, 924(2): 133140.
［6］	Chen L, Liu B. Relationships between stress granules, oxidative stress, and neurodegenerative diseases ［J］. Oxid Med Cell Longev, 2017, 2017: 1809592.
［7］	Han SH, Park JC, MookJung I. Amyloid βinteracting partners in Alzheimer's disease: From accomplices to possible therapeutic targets ［J］. Prog Neurobiol, 2016, 137: 1738.
［8］	张琴, 邝莹, 李峰. 姜黄素胶束对Aβ142诱导HT22细胞损伤的保护作用［J］. 解剖学研究, 2019, 41(2): 8187.
［9］	Zhong L, Tong Y, Chuan J, et al. Protective effect of ethyl vanillin against Aβinduced neurotoxicity in PC12 cells via the reduction of oxidative stress and apoptosis ［J］. Exp Ther Med, 2019, 17(4): 26662674.
［10］	Chen K, Lu Y, Liu C, et al. Morroniside prevents H2O2 or Aβinduced apoptosis via attenuating JNK and p38 MAPK phosphorylation ［J］. Eur J Pharmacol, 2018, 834: 295304.
［11］	刘东星. 京尼平苷对Aβ142诱导的SHSY5Y细胞的保护作用及相关机制研究［D］. 山西医科大学, 2019.
［12］	Khan M, Ullah R, Rehman SU, et al. 17βEstradiol modulates SIRT1 and halts oxidative stressmediated cognitive impairment in a male aging mouse model ［J］. Cells, 2019, 8(8): 928947.
［13］	Yang W, Shi L, Chen L, et al. Protective effects of perindopril on dgalactose and aluminum trichloride induced neurotoxicity via the apoptosis of mitochondriamediated intrinsic pathway in the hippocampus of mice ［J］. Brain Res Bull, 2014, 109: 4653.
［14］	Lian W, Jia H, Xu L, et al. Multiprotection of DL0410 in ameliorating cognitive defects in Dgalactose induced aging mice ［J］. Front Aging Neurosci, 2017, 9: 409425.
［15］	DukicStefanovic S, Schinzel R, Riederer P, et al. AGES in brain ageing: AGEinhibitors as neuroprotective and antidementia drugs ［J］? Biogerontology, 2001, 2(1): 1934.
［16］	Hsieh HM, Wu WM, Hu ML. Genistein attenuates Dgalactoseinduced oxidative damage through decreased reactive oxygen species and NFκB binding activity in neuronal PC12 cells ［J］. Life Sci, 2011, 88: 8288.
［17］	苗鑫, 张弘, 武燕, 等. 肉苁蓉毛蕊花糖苷对D半乳糖诱导PC12神经细胞损伤的保护作用［J］. 中国药学杂志, 2017, 52(23): 20712078.
［18］	Kaushal A, Wani WY, Bal A, et al. Okadaic acid and hypoxia induced dementia model of Alzheimer's type in rats ［J］. Neurotox Res, 2019, 35(3): 621634.
［19］	Hamidi N, Nozad A, Sheikhkanloui Milan H, et al. Okadaic acid attenuates shortterm and longterm synaptic plasticity of hippocampal dentate gyrus neurons in rats ［J］. Neurobiol Learn Mem, 2019, 158: 2431.
［20］	Kamat PK, Nath C. Okadaic acid: a tool to study regulatory mechanisms for neurodegeneration and regeneration in Alzheimer's disease ［J］. Neural Regen Res, 2015, 10(3): 365367.
［21］	Shen XY, Luo T, Li S, et al. Quercetin inhibits okadaic acidinduced tau protein hyperphosphorylation through the Ca2+calpainp25CDK5 pathway in HT22 cells ［J］. Int J Mol Med, 2018, 41(2): 11381146.
［22］	Huang L, Lin M, Zhong X, et al. Galangin decreases ptau, Aβ42 and βsecretase levels, and suppresses autophagy in okadaic acidinduced PC12 cells via an Akt/GSK3β/mTOR signalingdependent mechanism ［J］. Mol Med Report, 2019, 19(3): 17671774.
［23］	Ma XH, Duan WJ, Mo YS, et al. Neuroprotective effect of paeoniflorin on okadaic acidinduced tau hyperphosphorylation via calpain/Akt/GSK3β pathway in SHSY5Y cells ［J］. Brain Res, 2018, 1690: 111.
［24］	SabogalGuáqueta AM, Hobbie F, Keerthi A, et al. Linalool attenuates oxidative stress and mitochondrial dysfunction mediated by glutamate and NMDA toxicity ［J］. Biomed Pharmacother, 2019, 118: 109295.
［25］	Maher P, Van Leyen K, Dey PN, et al. The role of Ca2+ in cell death caused by oxidative glutamate toxicity and ferroptosis ［J］. Cell Calcium, 2018, 70: 4755.
［26］	Aman TK, Maki BA, Ruffino TJ, et al. Separate intramolecular targets for protein kinase A control NmethylDaspartate receptor gating and Ca2+ permeability ［J］. J Biol Chem, 2014, 289(27): 1880518817.
［27］	Zhang Y, Wang J, Wang C, et al. Pharmacological basis for the use of evodiamine in Alzheimer's disease: antioxidation and antiapoptosis ［J］. Int J Mol Sci, 2018, 19(5): 15271540.
［28］	Wang C, Cai X, Hu W, et al. Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with Alzheimer's disease ［J］. Int J Mol Med, 2019, 43(2): 956966.
［29］	Hu X, Qu Y, Chu Q, et al. Investigation of the neuroprotective effects of Lycium barbarum water extract in apoptotic cells and Alzheimer's disease mice ［J］. Mol Med Report, 2018, 17(3): 35993606.
［30］	Zhu X, Wang K, Zhang K, et al. Puerarin protects human neuroblastoma SHSY5Y cells against glutamateinduced oxidative stress and mitochondrial dysfunction ［J］. J Biochem Mol Toxicol, 2016, 30(1): 2228.
［31］	Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo ［J］. Science, 2005, 308(5726): 13141318.
［32］	Schmidt AF, Kannan PS, Chougnet CA, et al. Intraamniotic LPS causes acute neuroinflammation in preterm rhesus macaques ［J］. J Neuroinflammation, 2016, 13(1): 238247.
［33］	Lopes PC. LPS and neuroinflammation: a matter of timing ［J］. Inflammopharmacology, 2016, 24(5): 291293.
［34］	Askari VR, ShafieeNick R. The protective effects of βcaryophyllene on LPSinduced primary microglia M1/M2 imbalance: A mechanistic evaluation ［J］. Life Sci, 2019, 219: 4073.
［35］	Zhao Z, Xu Z, Liu T, et al. Human urinary kallidinogenase reduces lipopolysaccharideinduced neuroinflammation and oxidative stress in BV2 cells ［J］. Pain Res Manag, 2019, 2019: 6393150.
［36］	Bharathi, Shamasundar NM, Sathyanarayana Rao TS, et al. A new insight on Almaltolatetreated aged rabbit as Alzheimer's animal model ［J］. Brain Res Rev, 2006, 52(2): 275292.
［37］	Colomina MT, PerisSampedro F. Aluminum and Alzheimer's disease ［J］. Adv Neurobiol, 2017, 18: 183197.
［38］	Bharathi DM, JustinThenmozhi A, Manivasagam T, et al. Amelioration of Aluminum maltolateinduced inflammation and endoplasmic reticulum stressmediated apoptosis by tannoid principles of emblica officinalis in neuronal cellular model ［J］. Neurotox Res, 2019, 35(2): 318330.
［39］	Wang H, Shao B, Yu H, et al. Neuroprotective role of hyperforin on aluminum maltolateinduced oxidative damage and apoptosis in PC12 cells and SHSY5Y cells ［J］. ChemBiol Interact, 2019, 299: 1526.
［40］	Lee J, Giordano S, Zhang J. Autophagy, mitochondria and oxidative stress: crosstalk and redox signalling ［J］. Biochem J, 2012, 441(2): 523540.
［41］	Kushairi N, Phan CW, Sabaratnam V, et al. Lion's mane mushroom, hericium erinaceus (Bull.: Fr.) Pers. suppresses H2O2induced oxidative damage and LPSinduced inflammation in HT22 hippocampal neurons and BV2 microglia ［J］. Antioxidants (Basel), 2019, 8(8): 261279.
［42］	Liu S, Yu G, Song G, et al. Green tea polyphenols protect PC12 cells against H2O2induced damages by upregulating lncRNA MALAT1 ［J］. Int J Immunopathol Pharmacol, 2019, 33: 110.
［43］	Huang B, Liu J, Fu S, et al. αCyperone attenuates H2O2induced oxidative stress and apoptosis in SHSY5Y cells activation of Nrf2 ［J］. Front Pharmacol, 2020, 11: 281290.
［44］	Wei H, Gao Z, Zheng L, et al. Protective effects of fucoidan on Aβ2535 and dGalinduced neurotoxicity in PC12 cells and dGalinduced cognitive dysfunction in mice ［J］. Mar Drugs, 2017, 15(3): 7789.
［45］	魏恒云. Fucoidan对β淀粉样蛋白和Dgal联合诱导PC12细胞和小鼠学习记忆能力损伤的保护作用［D］. 大连医科大学, 2016.
［46］	Buendia I, Egea J, Parada E, et al. The melatoninN, Ndibenzyl (Nmethyl) amine hybrid ITH91/IQM157 affords neuroprotection in an in vitro Alzheimer's model via hemooxygenase1 induction ［J］. ACS Chem Neurosci, 2015, 6(2): 288296.
［47］	Che H, Zhou M, Zhang T, et al. Comparative study of the effects of phosphatidylcholine rich in DHA and EPA on Alzheimer's disease and the possible mechanisms in CHOAPP/PS1 cells and SAMP8 mice ［J］. Food Funct, 2018, 9(1): 643654.
［48］	Chiu YJ, Hsieh YH, Lin TH, et al. Novel compound VB037 inhibits Aβ aggregation and promotes neurite outgrowth through enhancement of HSP27 and reduction of P38 and JNKmediated inflammation in cell models for Alzheimer's disease ［J］. Neurochem Int, 2019, 125: 175186.
［49］	Li B, Zhao Y, Song M, et al. Role of cMyc/chloride intracellular channel 4 pathway in lipopolysaccharideinduced neurodegenerative diseases ［J］. Toxicology, 2020, 429: 152312.
［50］	方小霞, 周易, 孙高林, 等. TGFβ1对Aβ142诱导海马神经元小胶质细胞共培养体系中细胞因子表达和分泌的影响［J］. 中国应用生理学杂志, 2018, 34(5): 385388.
［51］	Jorfi M, D'avanzo C, Tanzi RE, et al. Human neurospheroid arrays for in vitro studies of Alzheimer's disease ［J］. Sci Rep, 2018, 8(1): 24502462.
［52］	Papadimitriou C, Celikkaya H, Cosacak MI, et al. 3D culture method for Alzheimer's disease modeling reveals Interleukin4 rescues Aβ42induced loss of human neural stem cell plasticity ［J］. Dev Cell, 2018, 46(1): 85101.
［53］	Osaki T, Shin Y, Sivathanu V, et al. In vitro microfluidic models for neurodegenerative disorders ［J］. Adv Healthc Mater, 2018, 7(2): 1700489.
［54］	Gao F, Gao K, He C, et al. Multisite dynamic recording for Aβ oligomersinduced Alzheimer's disease in vitro based on neuronal network chip ［J］. Biosens Bioelectron, 2019, 133: 183191.
［55］	Majolo F, Marinowic DR, Machado DC, et al. Important advances in Alzheimer's disease from the use of induced pluripotent stem cells ［J］. J Biomed Sci, 2019, 26(1): 1533.
［56］	Robbins JP, Price J. Human induced pluripotent stem cells as a research tool in Alzheimer's disease ［J］. Psychol Med, 2017, 47(15): 25872592.
［57］	Balez R, Steiner N, Engel M, et al. Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer's disease ［J］. Sci Rep, 2016, 6: 31450.
［58］	Zhao J, Zhang G, Li M, et al. Neuroprotective effects of aloperine in an Alzheimer's disease cellular model ［J］. Biomed Pharmacother, 2018, 108: 137143.
［59］	Zhang P, Kishimoto Y, Grammatikakis I, et al. Senolytic therapy alleviates Aβassociated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer's disease model ［J］. Nat Neurosci, 2019, 22(5): 719728.
［60］	Dezfulian M. A new Alzheimer's disease cell model using B cells to induce beta amyloid plaque formation and increase TNF alpha expression ［J］. Int Immunopharmacol, 2018, 59: 106112.
［61］	Liu B, Liu G, Wang Y, et al. Protective effect of Buyang Huanwu Decoction on neurovascular unit in Alzheimer's disease cell model via inflammation and RAGE/LRP1 pathway ［J］. Med Sci Monit, 2019, 25: 78137825.
［62］	Li H, Han W, Wang H, et al. Tanshinone IIA inhibits glutamateinduced oxidative toxicity through prevention of mitochondrial dysfunction and suppression of MAPK activation in SHSY5Y human neuroblastoma cells ［J］. Oxid Med Cell Longev, 2017, 2017: 4517486.

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[14]	NI Jian-liang, WANG Shui-hong, YANG Hua, CHEN Song, WEI Li-juan. A randomized double-blind control study on oxiracetam and donepezil in treating Alzheimer disease [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(11): 1291-1294.
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