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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

在阿尔茨海默病体外模型中，磷酸胆碱对淀粉样蛋白 β 神经毒性的有益作用

卷 18, 期 4, 2021

发表于: 23 September, 2021

页: [298 - 309] 页: 12

弟呕挨: 10.2174/1567205018666210608093658

价格: $65

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摘要

背景：阿尔茨海默病 (AD) 是最常见的以认知障碍为特征的神经退行性疾病，这是一个紧迫的公共卫生问题。鉴于 AD 的全球影响，迫切需要有效的疗法来减缓或阻止这种疾病。

目的：磷酸胆碱 (α-GPC) 是一种潜在有效的胆碱能神经传递增强剂，在改善认知功能障碍方面具有有趣的临床特征，尽管关于这种有益作用背后的机制的数据很少。

方法：将 SH-SY5Y 神经元细胞系用 10 μm 全反式维甲酸 (RA) 分化 1 周，以实现向胆碱能表型的转变，用作 AD 的体外模型。 SH-SY5Y细胞用α-GPC（100nM）预处理1小时，用Aβ25-35（10μM）处理72小时。

结果：α-GPC 能够拮抗 Aβ25-35 介导的神经毒性并减弱 Aβ 诱导的 Tau 蛋白磷酸化。此外，α-GPC 通过使用 NGF/TrkA 系统发挥其有益作用，在 AD 中被击倒，因此，通过维持突触囊泡蛋白（如突触素）的表达水平。

结论：综上所述，我们的数据表明，α-GPC 在 Aβ 毒性挑战过程中可以起到神经保护作用。因此，更深入地了解其有益作用的机制，可以为其功能性胆碱能增强的潜在未来药理学应用提供新的见解，旨在减轻 AD，并可能代表创新疗法的基础。

关键词: 乙酰胆碱、细胞凋亡、胆碱能神经传递、神经元、突触发生、阿尔茨海默病。

« Previous Next »
[1]
Forner S, Baglietto-Vargas D, Martini AC, Trujillo-Estrada L, LaFerla FM. Synaptic impairment in Alzheimer’s disease: A dysregulated symphony. Trends Neurosci 2017; 40(6): 347-57.
[http://dx.doi.org/10.1016/j.tins.2017.04.002] [PMID: 28494972]
[2]
Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell 2010; 140(6): 918-34.
[http://dx.doi.org/10.1016/j.cell.2010.02.016] [PMID: 20303880]
[3]
Arendt T, Brückner MK, Morawski M, Jäger C, Gertz H-J. Early neurone loss in Alzheimer’s disease: Cortical or subcortical? Acta Neuropathol Commun 2015; 3(1): 10.
[http://dx.doi.org/10.1186/s40478-015-0187-1] [PMID: 25853173]
[4]
Ballinger EC, Ananth M, Talmage DA, Role LW. Basal forebrain cholinergic circuits and signaling in cognition and cognitive decline. Neuron 2016; 91(6): 1199-218.
[http://dx.doi.org/10.1016/j.neuron.2016.09.006] [PMID: 27657448]
[5]
Cavedo E, Grothe MJ, Colliot O, et al. Reduced basal forebrain atrophy progression in a randomized Donepezil trial in prodromal Alzheimer’s disease. Sci Rep 2017; 7(1): 11706.
[http://dx.doi.org/10.1038/s41598-017-09780-3] [PMID: 28916821]
[6]
Bartus RT, Dean RL III, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982; 217(4558): 408-14.
[http://dx.doi.org/10.1126/science.7046051] [PMID: 7046051]
[7]
Guarnieri G, Sarchielli E, Vannelli GB, Morelli A. Cell-based therapy in Alzheimer’s disease: Can human fetal cholinergic neurons “untangle the skein”? Neural Regen Res 2018; 13(12): 2105-7.
[http://dx.doi.org/10.4103/1673-5374.241459] [PMID: 30323137]
[8]
Parnetti L, Mignini F, Tomassoni D, Traini E, Amenta F. Cholinergic precursors in the treatment of cognitive impairment of vascular origin: Ineffective approaches or need for re-evaluation? J Neurol Sci 2007; 257(1-2): 264-9.
[http://dx.doi.org/10.1016/j.jns.2007.01.043] [PMID: 17331541]
[9]
Scapicchio PL. Revisiting choline alphoscerate profile: A new, perspective, role in dementia? Int J Neurosci 2013; 123(7): 444-9.
[http://dx.doi.org/10.3109/00207454.2013.765870] [PMID: 23387341]
[10]
Tuboly E, Gáspár R, Ibor MO, et al. L-Alpha-glycerylphosphorylcholine can be cytoprotective or cytotoxic in neonatal rat cardiac myocytes: A double-edged sword phenomenon. Mol Cell Biochem 2019; 460(1-2): 195-203.
[http://dx.doi.org/10.1007/s11010-019-03580-1] [PMID: 31280435]
[11]
Traini E, Bramanti V, Amenta F. Choline alphoscerate (alpha-glyceryl-phosphoryl-choline) an old choline- containing phospholipid with a still interesting profile as cognition enhancing agent. Curr Alzheimer Res 2013; 10(10): 1070-9.
[http://dx.doi.org/10.2174/15672050113106660173] [PMID: 24156263]
[12]
Chen X-Q, Sawa M, Mobley WC. Dysregulation of neurotrophin signaling in the pathogenesis of Alzheimer disease and of Alzheimer disease in Down syndrome. Free Radic Biol Med 2018; 114: 52-61.
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.10.341] [PMID: 29031834]
[13]
Latina V, Caioli S, Zona C, Ciotti MT, Amadoro G, Calissano P. Impaired NGF/TrkA signaling causes early AD-linked presynaptic dysfunction in cholinergic primary neurons. Front Cell Neurosci 2017; 11: 68.
[http://dx.doi.org/10.3389/fncel.2017.00068] [PMID: 28360840]
[14]
Canu N, Amadoro G, Triaca V, et al. The intersection of NGF/TrkA signaling and amyloid precursor protein processing in Alzheimer’s disease neuropathology. Int J Mol Sci 2017; 18(6): E1319.
[http://dx.doi.org/10.3390/ijms18061319] [PMID: 28632177]
[15]
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-54.
[http://dx.doi.org/10.1016/0003-2697(76)90527-3] [PMID: 942051]
[16]
Cantarella G, Uberti D, Carsana T, Lombardo G, Bernardini R, Memo M. Neutralization of TRAIL death pathway protects human neuronal cell line from beta-amyloid toxicity. Cell Death Differ 2003; 10(1): 134-41.
[http://dx.doi.org/10.1038/sj.cdd.4401143] [PMID: 12655302]
[17]
Cantarella G, Lempereur L, D’Alcamo MA, et al. Trail interacts redundantly with nitric oxide in rat astrocytes: Potential contribution to neurodegenerative processes. J Neuroimmunol 2007; 182(1-2): 41-7.
[http://dx.doi.org/10.1016/j.jneuroim.2006.09.007] [PMID: 17067687]
[18]
Kyriakis JM, Avruch J. Mammalian MAPK signal transduction pathways activated by stress and inflammation: A 10-year update. Physiol Rev 2012; 92(2): 689-737.
[http://dx.doi.org/10.1152/physrev.00028.2011] [PMID: 22535895]
[19]
Palavicini JP, Wang C, Chen L, et al. Oligomeric amyloid-beta induces MAPK-mediated activation of brain cytosolic and calcium-independent phospholipase A2 in a spatial-specific manner. Acta Neuropathol Commun 2017; 5(1): 56.
[http://dx.doi.org/10.1186/s40478-017-0460-6] [PMID: 28750656]
[20]
Sigala S, Imperato A, Rizzonelli P, Casolini P, Missale C, Spano P. L-alpha-glycerylphosphorylcholine antagonizes scopolamine-induced amnesia and enhances hippocampal cholinergic transmission in the rat. Eur J Pharmacol 1992; 211(3): 351-8.
[http://dx.doi.org/10.1016/0014-2999(92)90392-H] [PMID: 1319912]
[21]
Lopez CM, Govoni S, Battaini F, et al. Effect of a new cognition enhancer, alpha-glycerylphosphorylcholine, on scopolamine-induced amnesia and brain acetylcholine. Pharmacol Biochem Behav 1991; 39(4): 835-40.
[http://dx.doi.org/10.1016/0091-3057(91)90040-9] [PMID: 1662399]
[22]
Parnetti L, Amenta F, Gallai V. Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: An analysis of published clinical data. Mech Ageing Dev 2001; 122(16): 2041-55.
[http://dx.doi.org/10.1016/S0047-6374(01)00312-8] [PMID: 11589921]
[23]
Amenta F, Tayebati SK, Vitali D, Di Tullio MA. Association with the cholinergic precursor choline alphoscerate and the cholinesterase inhibitor rivastigmine: An approach for enhancing cholinergic neurotransmission. Mech Ageing Dev 2006; 127(2): 173-9.
[http://dx.doi.org/10.1016/j.mad.2005.09.017] [PMID: 16297435]
[24]
Aleppo G, Nicoletti F, Sortino MA, Casabona G, Scapagnini U, Canonico PL. Chronic L-alpha-glyceryl-phosphoryl-choline increases inositol phosphate formation in brain slices and neuronal cultures. Pharmacol Toxicol 1994; 74(2): 95-100.
[http://dx.doi.org/10.1111/j.1600-0773.1994.tb01082.x] [PMID: 8190709]
[25]
Amenta F, Tayebati SK. Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction. Curr Med Chem 2008; 15(5): 488-98.
[http://dx.doi.org/10.2174/092986708783503203] [PMID: 18289004]
[26]
Catanesi M, d’Angelo M, Antonosante A, et al. Neuroprotective potential of choline alfoscerate against β-amyloid injury: Involvement of neurotrophic signals. Cell Biol Int 2020; 44(8): 1734-44.
[http://dx.doi.org/10.1002/cbin.11369] [PMID: 32343461]
[27]
Wang Y, Guan X, Chen X, et al. Choline supplementation ameliorates behavioral deficits and Alzheimer’s disease-like pathology in transgenic APP/PS1 mice. Mol Nutr Food Res 2019; 63(18): e1801407.
[http://dx.doi.org/10.1002/mnfr.201801407] [PMID: 31298459]
[28]
Anand P, Singh B. A review on cholinesterase inhibitors for Alzheimer’s disease. Arch Pharm Res 2013; 36(4): 375-99.
[http://dx.doi.org/10.1007/s12272-013-0036-3] [PMID: 23435942]
[29]
Adlimoghaddam A, Neuendorff M, Roy B, Albensi BC. A review of clinical treatment considerations of donepezil in severe Alzheimer’s disease. CNS Neurosci Ther 2018; 24(10): 876-88.
[http://dx.doi.org/10.1111/cns.13035] [PMID: 30058285]
[30]
Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM. Alzheimer’s disease: Targeting the cholinergic system. Curr Neuropharmacol 2016; 14(1): 101-15.
[http://dx.doi.org/10.2174/1570159X13666150716165726] [PMID: 26813123]
[31]
Di Santo SG, Prinelli F, Adorni F, Caltagirone C, Musicco M. A meta-analysis of the efficacy of donepezil, rivastigmine, galantamine, and memantine in relation to severity of Alzheimer’s disease. J Alzheimers Dis 2013; 35(2): 349-61.
[http://dx.doi.org/10.3233/JAD-122140] [PMID: 23411693]
[32]
Chen X-Q, Mobley WC. Exploring the pathogenesis of Alzheimer disease in basal forebrain cholinergic neurons: Converging insights from alternative hypotheses. Front Neurosci 2019; 13: 446.
[http://dx.doi.org/10.3389/fnins.2019.00446] [PMID: 31133787]
[33]
Knott V, de la Salle S, Choueiry J, et al. Neurocognitive effects of acute choline supplementation in low, medium and high performer healthy volunteers. Pharmacol Biochem Behav 2015; 131: 119-29.
[http://dx.doi.org/10.1016/j.pbb.2015.02.004] [PMID: 25681529]
[34]
Li K, Wei Q, Liu F-F, et al. Synaptic dysfunction in Alzheimer’s disease: Aβ, Tau, and epigenetic alterations. Mol Neurobiol 2018; 55(4): 3021-32.
[http://dx.doi.org/10.1007/s12035-017-0533-3] [PMID: 28456942]
[35]
Gao Y, Tan L, Yu J-T, Tan L. Tau in Alzheimer’s disease: Mechanisms and therapeutic strategies. Curr Alzheimer Res 2018; 15(3): 283-300.
[http://dx.doi.org/10.2174/1567205014666170417111859] [PMID: 28413986]
[36]
Molinuevo JL, Berthier ML, Rami L. Donepezil provides greater benefits in mild compared to moderate Alzheimer’s disease: Implications for early diagnosis and treatment. Arch Gerontol Geriatr 2011; 52(1): 18-22.
[http://dx.doi.org/10.1016/j.archger.2009.11.004] [PMID: 19948364]
[37]
Emery VOB. Alzheimer disease: Are we intervening too late? Pro. J Neural Transm (Vienna) 2011; 118(9): 1361-78.
[http://dx.doi.org/10.1007/s00702-011-0663-0] [PMID: 21647682]
[38]
Isaev NK, Stelmashook EV, Genrikhs EE. Role of nerve growth factor in plasticity of forebrain cholinergic neurons. Biochemistry (Mosc) 2017; 82(3): 291-300.
[http://dx.doi.org/10.1134/S0006297917030075] [PMID: 28320270]
[39]
Wiener CD, de Mello Ferreira S, Pedrotti Moreira F, et al. Serum levels of nerve growth factor (NGF) in patients with major depression disorder and suicide risk. J Affect Disord 2015; 184: 245-8.
[http://dx.doi.org/10.1016/j.jad.2015.05.067] [PMID: 26118751]
[40]
Neto FL, Borges G, Torres-Sanchez S, Mico JA, Berrocoso E. Neurotrophins role in depression neurobiology: A review of basic and clinical evidence. Curr Neuropharmacol 2011; 9(4): 530-52.
[http://dx.doi.org/10.2174/157015911798376262] [PMID: 22654714]
[41]
Cuello AC, Pentz R, Hall H. The brain NGF metabolic pathway in health and in Alzheimer’s pathology. Front Neurosci 2019; 13: 62.
[http://dx.doi.org/10.3389/fnins.2019.00062] [PMID: 30809111]
[42]
Sampaio TB, Savall AS, Gutierrez MEZ, Pinton S. Neurotrophic factors in Alzheimer’s and Parkinson’s diseases: Implications for pathogenesis and therapy. Neural Regen Res 2017; 12(4): 549-57.
[http://dx.doi.org/10.4103/1673-5374.205084] [PMID: 28553325]
[43]
Park H, Poo MM. Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci 2013; 14(1): 7-23.
[http://dx.doi.org/10.1038/nrn3379] [PMID: 23254191]
[44]
Xie Y, Tisi MA, Yeo TT, Longo FM. Nerve growth factor (NGF) loop 4 dimeric mimetics activate ERK and AKT and promote NGF-like neurotrophic effects. J Biol Chem 2000; 275(38): 29868-74.
[http://dx.doi.org/10.1074/jbc.M005071200] [PMID: 10896671]
[45]
Rai SN, Dilnashin H, Birla H, et al. The role of PI3K/Akt and ERK in neurodegenerative disorders. Neurotox Res 2019; 35(3): 775-95.
[http://dx.doi.org/10.1007/s12640-019-0003-y] [PMID: 30707354]
[46]
Falcicchia C, Tozzi F, Arancio O, Watterson DM, Origlia N. Involvement of p38 MAPK in synaptic function and dysfunction. Int J Mol Sci 2020; 21(16): E5624.
[http://dx.doi.org/10.3390/ijms21165624] [PMID: 32781522]
[47]
Asih PR, Prikas E, Stefanoska K, Tan ARP, Ahel HI, Ittner A. Functions of p38 MAP kinases in the central nervous system. Front Mol Neurosci 2020; 13: 570586.
[http://dx.doi.org/10.3389/fnmol.2020.570586] [PMID: 33013322]
[48]
Bell KFS, Claudio Cuello A. Altered synaptic function in Alzheimer’s disease. Eur J Pharmacol 2006; 545(1): 11-21.
[http://dx.doi.org/10.1016/j.ejphar.2006.06.045] [PMID: 16887118]
[49]
Gudi V, Gai L, Herder V, et al. Synaptophysin is a reliable marker for axonal damage. J Neuropathol Exp Neurol 2017; 76(2): 109-25.
[http://dx.doi.org/10.1093/jnen/nlw114] [PMID: 28177496]
[50]
Triaca V, Calissano P. Impairment of the nerve growth factor pathway driving amyloid accumulation in cholinergic neurons: The incipit of the Alzheimer’s disease story? Neural Regen Res 2016; 11(10): 1553-6.
[http://dx.doi.org/10.4103/1673-5374.193224] [PMID: 27904476]
[51]
De Jesus Moreno Moreno M. Cognitive improvement in mild to moderate Alzheimer’s dementia after treatment with the acetylcholine precursor choline alfoscerate: A multicenter, double-blind, randomized, placebo-controlled trial. Clin Ther 2003; 25(1): 178-93.
[http://dx.doi.org/10.1016/S0149-2918(03)90023-3] [PMID: 12637119]
[52]
Parnetti L, Abate G, Bartorelli L, et al. Multicentre study of l-alpha-glyceryl-phosphorylcholine vs ST200 among patients with probable senile dementia of Alzheimer’s type. Drugs Aging 1993; 3(2): 159-64.
[http://dx.doi.org/10.2165/00002512-199303020-00006] [PMID: 8477148]

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