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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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General Research Article

Protective Effects of Dendrobium nobile Lindl. Alkaloids on Alzheimer's Disease-like Symptoms Induced by High-methionine Diet

Author(s): Tingting Pi, Guangping Lang, Bo Liu and Jingshan Shi*

Volume 20, Issue 5, 2022

Published on: 29 March, 2022

Page: [983 - 997] Pages: 15

DOI: 10.2174/1570159X19666210809101945

Price: $65

Abstract

Background: High methionine-diet (HMD) causes Alzheimer's disease (AD)-like symptoms. Previous studies have shown that Dendrobium nobile Lindle. alkaloids (DNLA) have potential benefits for AD

Object: The objective of this study has been to explore whether DNLA can improve AD-like symptoms induced by HMD.

Methods: Mice were fed with 2% HMD diet for 11 weeks; the DNLA20 control group (20 mg/kg), DNLA10 group (10 mg/kg), and DNLA20 group (20 mg/kg) were administered DNLA for 3 months. Morris water maze test was used to detect learning and memory ability. Neuron damage was evaluated by HE and Nissl staining. Levels of homocysteine (Hcy), beta-amyloid 1-42 (Aβ1-42), S-adenosine methionine (SAM) and S-adenosine homocysteine (SAH) were detected by ELISA. Immunofluorescence and western blotting (WB) were used to determine the expression of proteins. CPG island methylation levels were accessed by Methylation-specific PCR (MSP) and MethylTarget methylation detection.

Results: Morris water maze test revealed that DNLA improved learning and memory dysfunction. HE, Nissl, and immunofluorescence staining showed that DNLA alleviated neuron damage and reduced the 5-methylcytosine (5-mC), Aβ1-40 and Aβ1-42 levels. DNLA also decreased the levels of Hcy and Aβ1-42 in the serum, along with decreasing SAM/SAH level in the liver tissue. WB results showed that DNLA down-regulated the expression of amyloid-precursor protein (APP), presenilin-1 (PS1), beta-secretase-1 (BACE1), DNA methyltransferase1 (DNMT1), Aβ1-40 and Aβ1-42 proteins. DNLA also up-regulated the proteins expression of insulin-degrading enzyme (IDE), neprilysin (NEP), DNMT3a and DNMT3b. Meanwhile, DNLA increased CPG island methylation levels of APP and BACE1 genes.

Conclusion: DNLA alleviated AD-like symptoms induced by HMD via the DNA methylation pathway.

Keywords: High methionine diet, Alzheimer's disease-like symptoms, DNA methylation, Dendrobium nobile Lindl. alkaloid, beta-amyloid, CPG.

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[1]
Lane, C.A.; Hardy, J.; Schott, J.M. Alzheimer’s disease. Eur. J. Neurol., 2018, 25(1), 59-70.
[http://dx.doi.org/10.1111/ene.13439] [PMID: 28872215]
[2]
Zhou, Y.; Shi, J.; Chu, D.; Hu, W.; Guan, Z.; Gong, C.X.; Iqbal, K.; Liu, F. Relevance of phosphorylation and truncation of tau to the etiopathogenesis of Alzheimer’s disease. Front. Aging Neurosci., 2018, 10, 27.
[http://dx.doi.org/10.3389/fnagi.2018.00027] [PMID: 29472853]
[3]
Theofilas, P.; Ehrenberg, A.J.; Nguy, A.; Thackrey, J.M.; Dunlop, S.; Mejia, M.B.; Alho, A.T.; Paraizo Leite, R.E.; Rodriguez, R.D.; Suemoto, C.K.; Nascimento, C.F.; Chin, M.; Medina-Cleghorn, D.; Cuervo, A.M.; Arkin, M.; Seeley, W.W.; Miller, B.L.; Nitrini, R.; Pasqualucci, C.A.; Filho, W.J.; Rueb, U.; Neuhaus, J.; Heinsen, H.; Grinberg, L.T. Probing the correlation of neuronal loss, neurofibrillary tangles, and cell death markers across the Alzheimer’s disease Braak stages: a quantitative study in humans. Neurobiol. Aging, 2018, 61, 1-12.
[http://dx.doi.org/10.1016/j.neurobiolaging.2017.09.007] [PMID: 29031088]
[4]
El Khoury, J.; Toft, M.; Hickman, S.E.; Means, T.K.; Terada, K.; Geula, C.; Luster, A.D. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat. Med., 2007, 13(4), 432-438.
[http://dx.doi.org/10.1038/nm1555] [PMID: 17351623]
[5]
Heneka, M.T.; Kummer, M.P.; Stutz, A.; Delekate, A.; Schwartz, S.; Vieira-Saecker, A.; Griep, A.; Axt, D.; Remus, A.; Tzeng, T.C.; Gelpi, E.; Halle, A.; Korte, M.; Latz, E.; Golenbock, D.T. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature, 2013, 493(7434), 674-678.
[http://dx.doi.org/10.1038/nature11729] [PMID: 23254930]
[6]
Zhou, H.Y.; Wu, W.J.; Xu, Y.Y.; Zhou, B.; Niu, K.; Liu, Z.Q.; Zheng, Y.G. Calcium carbonate addition improves l-methionine biosynthesis by metabolically engineered Escherichia coli W3110-BL. Front. Bioeng. Biotechnol., 2020, 8, 300.
[http://dx.doi.org/10.3389/fbioe.2020.00300] [PMID: 32426336]
[7]
Tapia-Rojas, C.; Lindsay, C.B.; Montecinos-Oliva, C.; Arrazola, M.S.; Retamales, R.M.; Bunout, D.; Hirsch, S.; Inestrosa, N.C. Is L-methionine a trigger factor for Alzheimer’s-like neurodegeneration?: Changes in Aβ oligomers, tau phosphorylation, synaptic proteins, Wnt signaling and behavioral impairment in wild-type mice. Mol. Neurodegener., 2015, 10, 62.
[http://dx.doi.org/10.1186/s13024-015-0057-0] [PMID: 26590557]
[8]
Cuello, A.C.; Hall, H.; Do Carmo, S. Experimental pharmacology in transgenic rodent models of Alzheimer’s disease. Front. Pharmacol., 2019, 10, 189.
[http://dx.doi.org/10.3389/fphar.2019.00189] [PMID: 30886583]
[9]
Zhang, N. Role of methionine on epigenetic modification of DNA methylation and gene expression in animals. Anim. Nutr., 2018, 4(1), 11-16.
[http://dx.doi.org/10.1016/j.aninu.2017.08.009] [PMID: 30167479]
[10]
Li, W.; Liu, H.; Yu, M.; Zhang, X.; Zhang, M.; Wilson, J.X.; Huang, G. Folic acid administration inhibits amyloid β-peptide accumulation in APP/PS1 transgenic mice. J. Nutr. Biochem., 2015, 26(8), 883-891.
[http://dx.doi.org/10.1016/j.jnutbio.2015.03.009] [PMID: 25959374]
[11]
Smith, A.D.; Refsum, H. Homocysteine, B vitamins, and cognitive impairment. Annu. Rev. Nutr., 2016, 36, 211-239.
[http://dx.doi.org/10.1146/annurev-nutr-071715-050947] [PMID: 27431367]
[12]
Moretti, R.; Caruso, P.; Dal Ben, M.; Conti, C.; Gazzin, S.; Tiribelli, C.; Vitamin, D. Vitamin D, homocysteine, and folate in subcortical vascular dementia and Alzheimer dementia. Front. Aging Neurosci., 2017, 9, 169.
[http://dx.doi.org/10.3389/fnagi.2017.00169] [PMID: 28611659]
[13]
Pi, T.; Liu, B.; Shi, J. Abnormal homocysteine metabolism: an insight of Alzheimer’s disease from DNA methylation. Behav. Neurol., 2020, 2020, 8438602.
[http://dx.doi.org/10.1155/2020/8438602] [PMID: 32963633]
[14]
Shirafuji, N.; Hamano, T.; Yen, S.H.; Kanaan, N.M.; Yoshida, H.; Hayashi, K.; Ikawa, M.; Yamamura, O.; Kuriyama, M.; Nakamoto, Y. Homocysteine increases tau phosphorylation, truncation and oligomerization. Int. J. Mol. Sci., 2018, 19(3), 891.
[http://dx.doi.org/10.3390/ijms19030891] [PMID: 29562600]
[15]
Zhuo, J.M.; Praticò, D. Severe in vivo hyper-homocysteinemia is not associatedwith elevation of amyloid-beta peptides in the Tg2576 mice. J. Alzheimers Dis., 2010, 21(1), 133-140.
[http://dx.doi.org/10.3233/JAD-2010-100171] [PMID: 20555139]
[16]
Shen, W.; Gao, C.; Cueto, R.; Liu, L.; Fu, H.; Shao, Y.; Yang, W.Y.; Fang, P.; Choi, E.T.; Wu, Q.; Yang, X.; Wang, H. Homocysteine-methionine cycle is a metabolic sensor system controlling methylation-regulated pathological signaling. Redox Biol., 2020, 28, 101322.
[http://dx.doi.org/10.1016/j.redox.2019.101322] [PMID: 31605963]
[17]
Reik, W.; Kelsey, G. Epigenetics: Cellular memory erased in human embryos. Nature, 2014, 511(7511), 540-541.
[http://dx.doi.org/10.1038/nature13648] [PMID: 25079550]
[18]
Luo, C.; Hajkova, P.; Ecker, J.R. Dynamic DNA methylation: In the right place at the right time. Science, 2018, 361(6409), 1336-1340.
[http://dx.doi.org/10.1126/science.aat6806] [PMID: 30262495]
[19]
Christopher, M.A.; Kyle, S.M.; Katz, D.J. Neuroepigenetic mechanisms in disease. Epigenetics Chromatin, 2017, 10(1), 47.
[http://dx.doi.org/10.1186/s13072-017-0150-4] [PMID: 29037228]
[20]
Frye, M.; Harada, B.T.; Behm, M.; He, C. RNA modifications modulate gene expression during development. Science, 2018, 361(6409), 1346-1349.
[http://dx.doi.org/10.1126/science.aau1646] [PMID: 30262497]
[21]
Yang, L.; Rau, R.; Goodell, M.A. DNMT3A in haematological malignancies. Nat. Rev. Cancer, 2015, 15(3), 152-165.
[http://dx.doi.org/10.1038/nrc3895] [PMID: 25693834]
[22]
Kinde, B.; Gabel, H.W.; Gilbert, C.S.; Griffith, E.C.; Greenberg, M.E. Reading the unique DNA methylation landscape of the brain: Non-CpG methylation, hydroxymethylation, and MeCP2. Proc. Natl. Acad. Sci. USA, 2015, 112(22), 6800-6806.
[http://dx.doi.org/10.1073/pnas.1411269112] [PMID: 25739960]
[23]
Du, J.; Johnson, L.M.; Jacobsen, S.E.; Patel, D.J. DNA methylation pathways and their crosstalk with histone methylation. Nat. Rev. Mol. Cell Biol., 2015, 16(9), 519-532.
[http://dx.doi.org/10.1038/nrm4043] [PMID: 26296162]
[24]
Yao, L.; Ye, Y.; Mao, H.; Lu, F.; He, X.; Lu, G.; Zhang, S. MicroRNA-124 regulates the expression of MEKK3 in the inflammatory pathogenesis of Parkinson’s disease. J. Neuroinflammation, 2018, 15(1), 13.
[http://dx.doi.org/10.1186/s12974-018-1053-4] [PMID: 29329581]
[25]
Lai, G.; Guo, Y.; Chen, D.; Tang, X.; Shuai, O.; Yong, T.; Wang, D.; Xiao, C.; Zhou, G.; Xie, Y.; Yang, B.B.; Wu, Q. Alcohol extracts from Ganoderma lucidum delay the progress of Alzheimer’s disease by regulating DNA methylation in rodents. Front. Pharmacol., 2019, 10, 272.
[http://dx.doi.org/10.3389/fphar.2019.00272] [PMID: 30971923]
[26]
Huo, Z.; Zhu, Y.; Yu, L.; Yang, J.; De Jager, P.; Bennett, D.A.; Zhao, J. DNA methylation variability in Alzheimer’s disease. Neurobiol. Aging, 2019, 76, 35-44.
[http://dx.doi.org/10.1016/j.neurobiolaging.2018.12.003] [PMID: 30660039]
[27]
Semick, S.A.; Bharadwaj, R.A.; Collado-Torres, L.; Tao, R.; Shin, J.H.; Deep-Soboslay, A.; Weiss, J.R.; Weinberger, D.R.; Hyde, T.M.; Kleinman, J.E.; Jaffe, A.E.; Mattay, V.S. Integrated DNA methylation and gene expression profiling across multiple brain regions implicate novel genes in Alzheimer’s disease. Acta Neuropathol., 2019, 137(4), 557-569.
[http://dx.doi.org/10.1007/s00401-019-01966-5] [PMID: 30712078]
[28]
Coppieters, N.; Dieriks, B.V.; Lill, C.; Faull, R.L.; Curtis, M.A.; Dragunow, M. Global changes in DNA methylation and hydroxymethylation in Alzheimer’s disease human brain. Neurobiol. Aging, 2014, 35(6), 1334-1344.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.11.031] [PMID: 24387984]
[29]
Li, S.; Zhou, J.; Xu, S.; Li, J.; Liu, J.; Lu, Y.; Shi, J.; Zhou, S.; Wu, Q. Induction of Nrf2 pathway by Dendrobium nobile Lindl. alkaloids protects against carbon tetrachloride induced acute liver injury. Biomed. Pharmacother., 2019, 117, 109073.
[http://dx.doi.org/10.1016/j.biopha.2019.109073] [PMID: 31212129]
[30]
Huang, S.; Wu, Q.; Liu, H.; Ling, H.; He, Y.; Wang, C.; Wang, Z.; Lu, Y.; Lu, Y. Alkaloids of dendrobium nobile lindl. Altered hepatic lipid homeostasis via regulation of bile acids. J. Ethnopharmacol., 2019, 241, 111976.
[http://dx.doi.org/10.1016/j.jep.2019.111976] [PMID: 31132462]
[31]
Huang, Q.; Liao, X.; Wu, Q.; Shi, J.S. Effects of total alkaloids of Dendrobium nobile Lindl. on GLUT4 expression in skeletal muscle of diabetic rats. Zhongguo Xin Yao Zazhi, 2019, 28(13), 1625-1628.
[32]
Xu, Y.Y.; Xu, Y.S.; Wang, Y.; Wu, Q.; Lu, Y.F.; Liu, J.; Shi, J.S. Dendrobium nobile Lindl. alkaloids regulate metabolism gene expression in livers of mice. J. Pharm. Pharmacol., 2017, 69(10), 1409-1417.
[http://dx.doi.org/10.1111/jphp.12778] [PMID: 28722145]
[33]
Nie, J.; Jiang, L.S.; Zhang, Y.; Tian, Y.; Li, L.S.; Lu, Y.L.; Yang, W.J.; Shi, J.S. Dendrobium nobile Lindl. Alkaloids decreases the level of intracellular β-Amyloid by improving impaired autolysosomal proteolysis in APP/PS1 mice. Front. Pharmacol., 2018, 9, 1479.
[http://dx.doi.org/10.3389/fphar.2018.01479] [PMID: 30618767]
[34]
Zhang, W.; Wu, Q.; Lu, Y.L.; Gong, Q.H.; Zhang, F.; Shi, J.S. Protective effects of Dendrobium nobile Lindl. alkaloids on amyloid beta (25-35)-induced neuronal injury. Neural Regen. Res., 2017, 12(7), 1131-1136.
[http://dx.doi.org/10.4103/1673-5374.211193] [PMID: 28852396]
[35]
Yang, S.; Gong, Q.; Wu, Q.; Li, F.; Lu, Y.; Shi, J. Alkaloids enriched extract from Dendrobium nobile Lindl. attenuates tau protein hyperphosphorylation and apoptosis induced by lipopolysaccharide in rat brain. Phytomedicine, 2014, 21(5), 712-716.
[http://dx.doi.org/10.1016/j.phymed.2013.10.026] [PMID: 24268296]
[36]
Huang, J.; Huang, N.; Zhang, M.; Nie, J.; Xu, Y.; Wu, Q.; Shi, J. Dendrobium alkaloids decrease Aβ by regulating α- and β-secretases in hippocampal neurons of SD rats. PeerJ, 2019, 7, e7627.
[http://dx.doi.org/10.7717/peerj.7627] [PMID: 31534855]
[37]
Liu, B.; Huang, B.; Liu, J.; Shi, J.S. Dendrobium nobile Lindl alkaloid and metformin ameliorate cognitive dysfunction in senescence-accelerated mice via suppression of endoplasmic reticulum stress. Brain Res., 2020, 1741, 146871.
[http://dx.doi.org/10.1016/j.brainres.2020.146871] [PMID: 32380088]
[38]
Mehla, J.; Lacoursiere, S.G.; Lapointe, V.; McNaughton, B.L.; Sutherland, R.J.; McDonald, R.J.; Mohajerani, M.H. Age-dependent behavioral and biochemical characterization of single APP knock-in mouse (APPNL-G-F/NL-G-F) model of Alzheimer’s disease. Neurobiol. Aging, 2019, 75, 25-37.
[http://dx.doi.org/10.1016/j.neurobiolaging.2018.10.026] [PMID: 30508733]
[39]
Vorhees, C.V.; Williams, M.T. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat. Protoc., 2006, 1(2), 848-858.
[http://dx.doi.org/10.1038/nprot.2006.116] [PMID: 17406317]
[40]
Velazquez, R.; Ferreira, E.; Knowles, S.; Fux, C.; Rodin, A.; Winslow, W.; Oddo, S. Lifelong choline supplementation ameliorates Alzheimer’s disease pathology and associated cognitive deficits by attenuating microglia activation. Aging Cell, 2019, 18(6), e13037.
[http://dx.doi.org/10.1111/acel.13037] [PMID: 31560162]
[41]
Nuru, M.; Muradashvili, N.; Kalani, A.; Lominadze, D.; Tyagi, N. High methionine, low folate and low vitamin B6/B12 (HM-LF-LV) diet causes neurodegeneration and subsequent short-term memory loss. Metab. Brain Dis., 2018, 33(6), 1923-1934.
[http://dx.doi.org/10.1007/s11011-018-0298-z] [PMID: 30094804]
[42]
Li, Y.; Li, F.; Gong, Q.; Wu, Q.; Shi, J. Inhibitory effects of Dendrobium alkaloids on memory impairment induced by lipopolysaccharide in rats. Planta Med., 2011, 77(2), 117-121.
[http://dx.doi.org/10.1055/s-0030-1250235] [PMID: 20717874]
[43]
Lv, L.L.; Liu, B.; Liu, J.; Li, L.S.; Jin, F.; Xu, Y.Y.; Wu, Q.; Liu, J.; Shi, J.S. Dendrobium nobile Lindl. Alkaloids ameliorate cognitive dysfunction in senescence accelerated SAMP8 mice by decreasing Amyloid-β aggregation and enhancing autophagy activity. J. Alzheimers Dis., 2020, 76(2), 657-669.
[http://dx.doi.org/10.3233/JAD-200308] [PMID: 32538851]
[44]
Hollands, C.; Tobin, M.K.; Hsu, M.; Musaraca, K.; Yu, T.S.; Mishra, R.; Kernie, S.G.; Lazarov, O. Depletion of adult neurogenesis exacerbates cognitive deficits in Alzheimer’s disease by compromising hippocampal inhibition. Mol. Neurodegener., 2017, 12(1), 64.
[http://dx.doi.org/10.1186/s13024-017-0207-7] [PMID: 28886753]
[45]
Hadipour, M.; Meftahi, G.H.; Afarinesh, M.R.; Jahromi, G.P.; Hatef, B. Crocin attenuates the granular cells damages on the dentate gyrus and pyramidal neurons in the CA3 regions of the hippocampus and frontal cortex in the rat model of Alzheimer’s disease. J. Chem. Neuroanat., 2021, 113, 101837.
[http://dx.doi.org/10.1016/j.jchemneu.2020.101837] [PMID: 32534024]
[46]
Pang, J.; Hou, J.; Zhou, Z.; Ren, M.; Mo, Y.; Yang, G.; Qu, Z.; Hu, Y. Safflower yellow improves synaptic plasticity in APP/PS1 mice by regulating microglia activation phenotypes and BDNF/TrkB/ERK signaling pathway. Neuromolecular Med., 2020, 22(3), 341-358.
[http://dx.doi.org/10.1007/s12017-020-08591-6] [PMID: 32048142]
[47]
Wang, Y.; Wang, M.; Fan, K.; Li, T.; Yan, T.; Wu, B.; Bi, K.; Jia, Y. Protective effects of Alpinae Oxyphyllae Fructus extracts on lipopolysaccharide-induced animal model of Alzheimer’s disease. J. Ethnopharmacol., 2018, 217, 98-106.
[http://dx.doi.org/10.1016/j.jep.2018.02.015] [PMID: 29447949]
[48]
Nie, J.; Tian, Y.; Zhang, Y.; Lu, Y.L.; Li, L.S.; Shi, J.S. Dendrobium alkaloids prevent Aβ25-35-induced neuronal and synaptic loss via promoting neurotrophic factors expression in mice. PeerJ, 2016, 4, e2739.
[http://dx.doi.org/10.7717/peerj.2739] [PMID: 27994964]
[49]
Kitsera, N.; Allgayer, J.; Parsa, E.; Geier, N.; Rossa, M.; Carell, T.; Khobta, A. Functional impacts of 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxycytosine at a single hemi-modified CpG dinucleotide in a gene promoter. Nucleic Acids Res., 2017, 45(19), 11033-11042.
[http://dx.doi.org/10.1093/nar/gkx718] [PMID: 28977475]
[50]
Chouliaras, L.; Mastroeni, D.; Delvaux, E.; Grover, A.; Kenis, G.; Hof, P.R.; Steinbusch, H.W.; Coleman, P.D.; Rutten, B.P.; van den Hove, D.L. Consistent decrease in global DNA methylation and hydroxymethylation in the hippocampus of Alzheimer’s disease patients. Neurobiol. Aging, 2013, 34(9), 2091-2099.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.02.021] [PMID: 23582657]
[51]
Liu, H.; Qiu, H.; Yang, J.; Ni, J.; Le, W. Chronic hypoxia facilitates Alzheimer’s disease through demethylation of γ-secretase by downregulating DNA methyltransferase 3b. Alzheimers Dement., 2016, 12(2), 130-143.
[http://dx.doi.org/10.1016/j.jalz.2015.05.019] [PMID: 26121910]
[52]
Bihaqi, S.W.; Zawia, N.H. Alzheimer’s disease biomarkers and epigenetic intermediates following exposure to Pb in vitro. Curr. Alzheimer Res., 2012, 9(5), 555-562.
[http://dx.doi.org/10.2174/156720512800617964] [PMID: 22272629]
[53]
Mata-Balaguer, T.; Cuchillo-Ibañez, I.; Calero, M.; Ferrer, I.; Sáez-Valero, J. Decreased generation of C-terminal fragments of ApoER2 and increased reelin expression in Alzheimer’s disease. FASEB J., 2018, 32(7), 3536-3546.
[http://dx.doi.org/10.1096/fj.201700736RR] [PMID: 29442527]
[54]
Kamat, P.K.; Kalani, A.; Tyagi, S.C.; Tyagi, N. Hydrogen sulfide epigenetically attenuates homocysteine-induced mitochondrial toxicity mediated through NMDA receptor in mouse brain endothelial (bEnd3) cells. J. Cell. Physiol., 2015, 230(2), 378-394.
[http://dx.doi.org/10.1002/jcp.24722] [PMID: 25056869]
[55]
Farina, N.; Jernerén, F.; Turner, C.; Hart, K.; Tabet, N. Homocysteine concentrations in the cognitive progression of Alzheimer’s disease. Exp. Gerontol., 2017, 99, 146-150.
[http://dx.doi.org/10.1016/j.exger.2017.10.008] [PMID: 29024723]
[56]
Obersby, D.; Chappell, D.C.; Dunnett, A.; Tsiami, A.A. Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis. Br. J. Nutr., 2013, 109(5), 785-794.
[http://dx.doi.org/10.1017/S000711451200520X] [PMID: 23298782]
[57]
Zhou, F.; Chen, S. Hyperhomocysteinemia and risk of incident cognitive outcomes: An updated dose-response meta-analysis of prospective cohort studies. Ageing Res. Rev., 2019, 51, 55-66.
[http://dx.doi.org/10.1016/j.arr.2019.02.006] [PMID: 30826501]
[58]
Di Meco, A.; Li, J.G.; Praticò, D. Dissecting the role of 5-Lipoxygenase in the homocysteine-induced Alzheimer’s disease pathology. J. Alzheimers Dis., 2018, 62(3), 1337-1344.
[http://dx.doi.org/10.3233/JAD-170700] [PMID: 29254095]
[59]
Yu, L.; Petyuk, V.A.; Tasaki, S.; Boyle, P.A.; Gaiteri, C.; Schneider, J.A.; De Jager, P.L.; Bennett, D.A. Association of cortical β-Amyloid protein in the absence of insoluble deposits with alzheimer disease. JAMA Neurol., 2019, 76(7), 818-826.
[http://dx.doi.org/10.1001/jamaneurol.2019.0834] [PMID: 31009033]
[60]
Sevigny, J.; Chiao, P.; Bussière, T.; Weinreb, P.H.; Williams, L.; Maier, M.; Dunstan, R.; Salloway, S.; Chen, T.; Ling, Y.; O’Gorman, J.; Qian, F.; Arastu, M.; Li, M.; Chollate, S.; Brennan, M.S.; Quintero-Monzon, O.; Scannevin, R.H.; Arnold, H.M.; Engber, T.; Rhodes, K.; Ferrero, J.; Hang, Y.; Mikulskis, A.; Grimm, J.; Hock, C.; Nitsch, R.M.; Sandrock, A. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature, 2016, 537(7618), 50-56.
[http://dx.doi.org/10.1038/nature19323] [PMID: 27582220]
[61]
Cai, Q.; Tammineni, P. Mitochondrial aspects of synaptic dysfunction in Alzheimer’s disease. J. Alzheimers Dis., 2017, 57(4), 1087-1103.
[http://dx.doi.org/10.3233/JAD-160726] [PMID: 27767992]
[62]
Sagare, A.P.; Bell, R.D.; Zhao, Z.; Ma, Q.; Winkler, E.A.; Ramanathan, A.; Zlokovic, B.V. Pericyte loss influences Alzheimer-like neurodegeneration in mice. Nat. Commun., 2013, 4, 2932.
[http://dx.doi.org/10.1038/ncomms3932] [PMID: 24336108]
[63]
Michno, W.; Nyström, S.; Wehrli, P.; Lashley, T.; Brinkmalm, G.; Guerard, L.; Syvänen, S.; Sehlin, D.; Kaya, I.; Brinet, D.; Nilsson, K.P.R.; Hammarström, P.; Blennow, K.; Zetterberg, H.; Hanrieder, J. Pyroglutamation of amyloid-βx-42 (Aβx-42) followed by Aβ1-40 deposition underlies plaque polymorphism in progressing Alzheimer’s disease pathology. J. Biol. Chem., 2019, 294(17), 6719-6732.
[http://dx.doi.org/10.1074/jbc.RA118.006604] [PMID: 30814252]
[64]
Nigam, S.M.; Xu, S.; Kritikou, J.S.; Marosi, K.; Brodin, L.; Mattson, M.P. Exercise and BDNF reduce Aβ production by enhancing α-secretase processing of APP. J. Neurochem., 2017, 142(2), 286-296.
[http://dx.doi.org/10.1111/jnc.14034] [PMID: 28382744]
[65]
Sun, L.; Zhou, R.; Yang, G.; Shi, Y. Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Aβ42 and Aβ40 peptides by γ-secretase. Proc. Natl. Acad. Sci. USA, 2017, 114(4), E476-E485.
[http://dx.doi.org/10.1073/pnas.1618657114] [PMID: 27930341]
[66]
Bossak-Ahmad, K.; Mital, M.; Płonka, D.; Drew, S.C.; Bal, W. Oligopeptides generated by neprilysin degradation of β-Amyloid have the highest Cu(II) affinity in the whole Aβ family. Inorg. Chem., 2019, 58(1), 932-943.
[http://dx.doi.org/10.1021/acs.inorgchem.8b03051] [PMID: 30582328]
[67]
Kurochkin, I.V.; Guarnera, E.; Berezovsky, I.N. Insulin-degrading enzyme in the fight against Alzheimer’s disease. Trends Pharmacol. Sci., 2018, 39(1), 49-58.
[http://dx.doi.org/10.1016/j.tips.2017.10.008] [PMID: 29132916]
[68]
Iwata, A.; Nagata, K.; Hatsuta, H.; Takuma, H.; Bundo, M.; Iwamoto, K.; Tamaoka, A.; Murayama, S.; Saido, T.; Tsuji, S. Altered CpG methylation in sporadic Alzheimer’s disease is associated with APP and MAPT dysregulation. Hum. Mol. Genet., 2014, 23(3), 648-656.
[http://dx.doi.org/10.1093/hmg/ddt451] [PMID: 24101602]
[69]
Schupf, N.; Zigman, W.B.; Tang, M.X.; Pang, D.; Mayeux, R.; Mehta, P.; Silverman, W. Change in plasma Aß peptides and onset of dementia in adults with Down syndrome. Neurology, 2010, 75(18), 1639-1644.
[http://dx.doi.org/10.1212/WNL.0b013e3181fb448b] [PMID: 21041786]
[70]
Kim, Y.E.; Cho, H.; Kim, H.J.; Na, D.L.; Seo, S.W.; Ki, C.S. PSEN1 variants in Korean patients with clinically suspicious early-onset familial Alzheimer’s disease. Sci. Rep., 2020, 10(1), 3480.
[http://dx.doi.org/10.1038/s41598-020-59829-z] [PMID: 32103039]
[71]
West, R.L.; Lee, J.M.; Maroun, L.E. Hypomethylation of the amyloid precursor protein gene in the brain of an Alzheimer’s disease patient. J. Mol. Neurosci., 1995, 6(2), 141-146.
[http://dx.doi.org/10.1007/BF02736773] [PMID: 8746452]
[72]
Huang, P.; Sun, J.; Wang, F.; Luo, X.; Zhu, H.; Gu, Q.; Sun, X.; Liu, T.; Sun, X. DNMT1 and Sp1 competitively regulate the expression of BACE1 in A2E-mediated photo-oxidative damage in RPE cells. Neurochem. Int., 2018, 121, 59-68.
[http://dx.doi.org/10.1016/j.neuint.2018.09.001] [PMID: 30273642]
[73]
Wang, S.C.; Oelze, B.; Schumacher, A. Age-specific epigenetic drift in late-onset Alzheimer’s disease. PLoS One, 2008, 3(7), e2698.
[http://dx.doi.org/10.1371/journal.pone.0002698] [PMID: 18628954]
[74]
Bourke, L.M.; Del Monte-Nieto, G.; Outhwaite, J.E.; Bharti, V.; Pollock, P.M.; Simmons, D.G.; Adam, A.; Hur, S.S.; Maghzal, G.J.; Whitelaw, E.; Stocker, R.; Suter, C.M.; Harvey, R.P.; Harten, S.K. Loss of Rearranged L-Myc Fusion (RLF) results in defects in heart development in the mouse. Differentiation, 2017, 94, 8-20.
[http://dx.doi.org/10.1016/j.diff.2016.11.004] [PMID: 27930960]

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