Research article Special Issues

Brain proteomics links oxidative stress with metabolic and cellular stress response proteins in behavioural alteration of Alzheimer’s disease model rats

  • Received: 29 August 2019 Accepted: 28 October 2019 Published: 15 November 2019
  • Alzheimer’s disease (AD) impairs memory and learning related behavioural performances of the affected person. Compared with the controls, memory and learning related behavioural performances of the AD model rats followed by hippocampal proteomics had been observed in the present study. In the eight armed radial maze, altered performance of the AD rats had been observed. Using liquid chromatography coupled tandem mass spectrometry (LC-MS/MS), 822 proteins had been identified with protein threshold at 95.0%, minimum peptide of 2 and peptide threshold at 0.1% FDR. Among them, 329 proteins were differentially expressed with statistical significance (P < 0.05). Among the significantly regulated (P < 0.05) 329 proteins, 289 met the criteria of fold change (LogFC of 1.5) cut off value. Number of proteins linked with AD, oxidative stress (OS) and hypercholesterolemia was 59, 20 and 12, respectively. Number of commonly expressed proteins was 361. The highest amount of proteins differentially expressed in the AD rats were those involved in metabolic processes followed by those linked with OS. Most notable was the perturbed state of the cholesterol metabolizing proteins in the AD group. Current findings suggest that proteins associated with oxidative stress, glucose and cholesterol metabolism and cellular stress response are among the mostly affected proteins in AD subjects. Thus, novel therapeutic approaches targeting these proteins could be strategized to withstand the ever increasing global AD burden.

    Citation: Mohammad Azizur Rahman, Shahdat Hossain, Noorlidah Abdullah, Norhaniza Aminudin. Brain proteomics links oxidative stress with metabolic and cellular stress response proteins in behavioural alteration of Alzheimer’s disease model rats[J]. AIMS Neuroscience, 2019, 6(4): 299-315. doi: 10.3934/Neuroscience.2019.4.299

    Related Papers:

  • Alzheimer’s disease (AD) impairs memory and learning related behavioural performances of the affected person. Compared with the controls, memory and learning related behavioural performances of the AD model rats followed by hippocampal proteomics had been observed in the present study. In the eight armed radial maze, altered performance of the AD rats had been observed. Using liquid chromatography coupled tandem mass spectrometry (LC-MS/MS), 822 proteins had been identified with protein threshold at 95.0%, minimum peptide of 2 and peptide threshold at 0.1% FDR. Among them, 329 proteins were differentially expressed with statistical significance (P < 0.05). Among the significantly regulated (P < 0.05) 329 proteins, 289 met the criteria of fold change (LogFC of 1.5) cut off value. Number of proteins linked with AD, oxidative stress (OS) and hypercholesterolemia was 59, 20 and 12, respectively. Number of commonly expressed proteins was 361. The highest amount of proteins differentially expressed in the AD rats were those involved in metabolic processes followed by those linked with OS. Most notable was the perturbed state of the cholesterol metabolizing proteins in the AD group. Current findings suggest that proteins associated with oxidative stress, glucose and cholesterol metabolism and cellular stress response are among the mostly affected proteins in AD subjects. Thus, novel therapeutic approaches targeting these proteins could be strategized to withstand the ever increasing global AD burden.


    加载中

    Acknowledgments



    The authors gratefully thank University of Malaya and the Ministry of Higher Education, Malaysia for the HIR-MOHE Research Grant F000002-21001 funding and Mohammad Azizur Rahman is grateful for the grant-in-aid provided by Jahangirnagar University and the University Grants Commission of Bangladesh.

    Conflict of interest



    The author reports no conflicts of interest and has received no payment in preparation of this manuscript.

    [1] Reiman EM (2014) Alzheimer's disease and other dementias: advances in 2013. Lancet Neurol 13: 3–5. doi: 10.1016/S1474-4422(13)70257-6
    [2] Liao L, Cheng D, Wang J, et al. (2004) Proteomic characterization of postmortem amyloid plaques isolated by laser capture microdissection. J Biol Chem 279: 37061–37068. doi: 10.1074/jbc.M403672200
    [3] Wang Q, Wu J, Rowan MJ, et al. (2005) β‐amyloid inhibition of long‐term potentiation is mediated via tumor necrosis factor. Eur J Neurosci 22: 2827–2832. doi: 10.1111/j.1460-9568.2005.04457.x
    [4] Lecanu L, Papadopoulos V (2013) Modeling Alzheimer's disease with non-transgenic rat models. Alzheimers Res Ther 5: 17.
    [5] Sparks DL, Scheff SW, Hunsaker JC, et al. (1994) Induction of Alzheimer-like β-amyloid immunoreactivity in the brains of rabbits with dietary cholesterol. Exp Neurol 126: 88–94. doi: 10.1006/exnr.1994.1044
    [6] Refolo LM, Malester B, LaFrancois J, et al. (2000) Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiol Dis 7: 321–331. doi: 10.1006/nbdi.2000.0304
    [7] Anstey KJ, Lipnicki DM, Low LF (2008) Cholesterol as a risk factor for dementia and cognitive decline: A systematic review of prospective studies with meta-analysis. Am J Geriatr Psychiatry 16: 343–354. doi: 10.1097/01.JGP.0000310778.20870.ae
    [8] Ansari MA, Scheff SW (2010) Oxidative stress in the progression of Alzheimer disease in the frontal cortex. J Neuropathol Exp Neurol 69: 155–167. doi: 10.1097/NEN.0b013e3181cb5af4
    [9] McLellan ME, Kajdasz ST, Hyman BT, et al. (2003) In vivo imaging of reactive oxygen species specifically associated with thioflavine S-positive amyloid plaques by multiphoton microscopy. J Neurosci 23: 2212–2217. doi: 10.1523/JNEUROSCI.23-06-02212.2003
    [10] Li F, Calingasan NY, Yu F, et al. (2004) Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice. J Neurochem 89: 1308–1312. doi: 10.1111/j.1471-4159.2004.02455.x
    [11] Dumont M, Wille E, Stack C, et al. (2009) Reduction of oxidative stress, amyloid deposition, and memory deficit by manganese superoxide dismutase overexpression in a transgenic mouse model of Alzheimer's disease. FASEB J 23: 2459–2466. doi: 10.1096/fj.09-132928
    [12] Murakami K, Murata N, Noda Y, et al. (2011) SOD1 (copper/zinc superoxide dismutase) deficiency drives amyloid β protein oligomerization and memory loss in mouse model of Alzheimer disease. J Biol Chem 286: 44557–44568. doi: 10.1074/jbc.M111.279208
    [13] Dröge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82: 47–95. doi: 10.1152/physrev.00018.2001
    [14] Tramutola A, Lanzillotta C, Perluigi M, et al. (2017) Butterfield, Oxidative stress, protein modification and Alzheimer disease. Brain Res Bull 133: 88–99. doi: 10.1016/j.brainresbull.2016.06.005
    [15] Mamun AA, Hashimoto M, Katakura M, et al. (2014) neuroprotective effect of madecassoside evaluated using amyloid Β 1-42 -mediated in vitro and in vivo Alzheimer's disease models. Intl J Indigenous Med Plants 47: 1669–1682.
    [16] Olton DS, Samuelson RJ (1976) Remembrance of places passed: spatial memory in rats. J Exp Psychol Anim Behav Process 2: 97–116. doi: 10.1037/0097-7403.2.2.97
    [17] Jarrard LE, Okaichi H, Steward O, et al. (1984) On the role of hippocampal connections in the performance of place and cue tasks: comparisons with damage to hippocampus. Behav Neurosci 98: 946–954. doi: 10.1037/0735-7044.98.6.946
    [18] Shevchenko G, Sjödin MO, Malmström D, et al. (2010) Cloud-point extraction and delipidation of porcine brain proteins in combination with bottom-up mass spectrometry approaches for proteome analysis. J Proteome Res 9: 3903–3911. doi: 10.1021/pr100116k
    [19] Stepanichev MY, Zdobnova IM, Zarubenko II, et al. (2007) Studies of the effects of central administration of β-amyloid peptide (25–35): pathomorphological changes in the hippocampus and impairment of spatial memory. Neurosci Behav Physiol 36: 101–106.
    [20] Holscher C, Gengler S, Gault VA, et al. (2007) Soluble beta-amyloid[25-35] reversibly impairs hippocampal synaptic plasticity and spatial learning. Eur J Pharmacol 561: 85–90. doi: 10.1016/j.ejphar.2007.01.040
    [21] Parihar MS, Brewer GJ (2007) Mitoenergetic failure in Alzheimer disease. Am J Physiol Cell Physiol 292: C8–C23. doi: 10.1152/ajpcell.00232.2006
    [22] Butterfield DA, Hardas SS, Lange ML (2010) Oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Alzheimer's disease: many pathways to neurodegeneration. J Alzheimers Dis 20: 369–393. doi: 10.3233/JAD-2010-1375
    [23] Minjarez B, Valero Rustarazo ML, Sanchez del Pino MM, et al. (2013) Identification of polypeptides in neurofibrillary tangles and total homogenates of brains with Alzheimer's disease by tandem mass spectrometry. J Alzheimers Dis 34: 239–262. doi: 10.3233/JAD-121480
    [24] Musunuri S, Wetterhall M, Ingelsson M, et al. (2014) Quantification of the brain proteome in Alzheimer's disease using multiplexed mass spectrometry. J Proteome Res 13: 2056–2068. doi: 10.1021/pr401202d
    [25] Butterfield DA, Perluigi M, Reed T, et al. (2012) Redox proteomics in selected neurodegenerative disorders: from its infancy to future applications. Antioxid Redox Signal 17: 1610–1655. doi: 10.1089/ars.2011.4109
    [26] Poon HF, Calabrese V, Calvani M, et al. (2006) Proteomics analyses of specific protein oxidation and protein expression in aged rat brain and its modulation by L-acetylcarnitine: insights into the mechanisms of action of this proposed therapeutic agent for CNS disorders associated with oxidative stress. Antioxid Redox Signal 8: 381–394. doi: 10.1089/ars.2006.8.381
    [27] Díez‐Vives C, Gay M, García‐Matas S, et al. (2009) Proteomic study of neuron and astrocyte cultures from senescence‐accelerated mouse SAMP8 reveals degenerative changes. J Neurochem 111: 945–955. doi: 10.1111/j.1471-4159.2009.06374.x
    [28] Blair LJ, Zhang B, Dickey CA (2013) Potential synergy between tau aggregation inhibitors and tau chaperone modulators. Alzheimers Res Ther 5: 41–50. doi: 10.1186/alzrt207
    [29] Yao J, Irwin RW, Zhao L, et al. (2009) Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease. PNAS 106: 14670–14675. doi: 10.1073/pnas.0903563106
    [30] Cui Y, Huang M, He Y, et al. (2011) Genetic ablation of apolipoprotein A-IV accelerates Alzheimer's disease pathogenesis in a mouse model. Am J Pathol 178: 1298–1308. doi: 10.1016/j.ajpath.2010.11.057
    [31] Keeney JTR, Swomley AM, Förster S, et al. (2013) Apolipoprotein A‐I: Insights from redox proteomics for its role in neurodegeneration. Proteomics Clin Appl 7: 109–122. doi: 10.1002/prca.201200087
    [32] Liu HC, Hu CJ, Chang JG, et al. (2006) Proteomic identification of lower apolipoprotein AI in Alzheimer's disease. Dement Geriatr Cogn Disord 21: 155–161. doi: 10.1159/000090676
    [33] Corder EH, Saunders AM, Strittmatter WJ, et al. (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261: 921–923. doi: 10.1126/science.8346443
    [34] Sizova D, Charbaut E, Delalande F, et al. (2007) Proteomic analysis of brain tissue from an Alzheimer's disease mouse model by two-dimensional difference gel electrophoresis. Neurobiol Aging 28: 357–370. doi: 10.1016/j.neurobiolaging.2006.01.011
    [35] Ellis RJ, Olichney JM, Thal LJ, et al. (1996) Cerebral amyloid angiopathy in the brains of patients with Alzheimer's disease: The CERAD experience, part XV. Neurology 46: 1592–1596. doi: 10.1212/WNL.46.6.1592
    [36] Kim J, Basak JM, Holtzman DM (2009) The role of apolipoprotein E in Alzheimer's disease. Neuron 63: 287–303. doi: 10.1016/j.neuron.2009.06.026
    [37] Choi J, Gao J, Kim J, et al. (2015) The E3 ubiquitin ligase Idol controls brain LDL receptor expression, ApoE clearance, and Aβ amyloidosis. Sci Transl Med 7: 314ra184.
    [38] Tosto G, Reitz C (2013) Genome-wide association studies in Alzheimer's disease: A review. Curr Neurol Neurosci Rep 13: 381. doi: 10.1007/s11910-013-0381-0
    [39] Yu JT, Tan L (2012) The role of clusterin in Alzheimer's disease: pathways, pathogenesis and therapy. Mol Neurobiol 45: 314–326. doi: 10.1007/s12035-012-8237-1
    [40] Hong I, Kang T, Yoo Y, et al. (2013) Quantitative proteomic analysis of the hippocampus in the 5XFAD mouse model at early stages of Alzheimer's disease pathology. J Alzheimers Dis 36: 321–334. doi: 10.3233/JAD-130311
    [41] Puglielli L, Konopka G, Pack-Chung E, et al. (2001) Acyl-coenzyme A: cholesterol acyltransferase modulates the generation of the amyloid β-peptide. Nat Cell Biol 3: 905–912. doi: 10.1038/ncb1001-905
    [42] Sjögren M, Mielke M, Gustafson D, et al. (2006) Cholesterol and Alzheimer's disease-is there a relation? Mech Ageing Dev 127: 138–147. doi: 10.1016/j.mad.2005.09.020
    [43] Cortes-Canteli M, Zamolodchikov D, Ahn HJ, et al. (2012) Fibrinogen and altered hemostasis in Alzheimer's disease. J Alzheimers Dis 32: 599–608. doi: 10.3233/JAD-2012-120820
    [44] Ahn HJ, Zamolodchikov D, Cortes-Canteli M, et al. (2010) Alzheimer's disease peptide β-amyloid interacts with fibrinogen and induces its oligomerization. Proc Natl Acad Sci U S A 107: 21812–21817. doi: 10.1073/pnas.1010373107
    [45] Li X, Buxbaum JN (2011) Transthyretin and the brain re-visited: Is neuronal synthesis of transthyretin protective in Alzheimer's disease? Mol Neurodegener 6: 79. doi: 10.1186/1750-1326-6-79
    [46] Flynn JM, Melov S (2013) SOD2 in mitochondrial dysfunction and neurodegeneration. Free Radic Biol Med 62: 4–12. doi: 10.1016/j.freeradbiomed.2013.05.027
    [47] De Leo ME, Borrello S, Passantino M, et al. (1998) Oxidative stress and overexpression of manganese superoxide dismutase in patients with Alzheimer's disease. Neurosci Lett 250: 173–176. doi: 10.1016/S0304-3940(98)00469-8
    [48] Manavalan A, Mishra M, Sze SK, et al. (2013) Brain-site-specific proteome changes induced by neuronal P60TRP expression. Neurosignals 21: 129–149. doi: 10.1159/000343672
    [49] Sun KH, Chang KH, Clawson S, et al. (2011) Glutathione‐S‐transferase P1 is a critical regulator of Cdk5 kinase activity. J Neurochem 118: 902–914. doi: 10.1111/j.1471-4159.2011.07343.x
    [50] Luo J, Wärmländer SKTS, Gräslund A, et al. (2014) Non-chaperone proteins can inhibit aggregation and cytotoxicity of Alzheimer amyloid β peptide. J Biol Chem 289: 27766–27775. doi: 10.1074/jbc.M114.574947
    [51] Habib KL, Lee TCM, Yang J (2010) Inhibitors of catalase-amyloid interactions protect cells from β-amyloid-induced oxidative stress and toxicity. J Biol Chem 285: 38933–38943. doi: 10.1074/jbc.M110.132860
    [52] Cocciolo A, Di Domenico F, Coccia R, et al. (2012) Decreased expression and increased oxidation of plasma haptoglobin in Alzheimer disease: Insights from redox proteomics. Free Radic Biol Med 53: 1868–1876. doi: 10.1016/j.freeradbiomed.2012.08.596
    [53] Spagnuolo MS, Maresca B, La Marca V, et al. (2014) Haptoglobin interacts with apolipoprotein E and beta-amyloid and influences their crosstalk. ACS Chem Neurosci 5: 837–847. doi: 10.1021/cn500099f
    [54] Poynton AR, Hampton MB (2014) Peroxiredoxins as biomarkers of oxidative stress. Biochim Biophys Acta 1840: 906–912. doi: 10.1016/j.bbagen.2013.08.001
  • neurosci-06-04-299-s001.pdf
  • Reader Comments
  • © 2019 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(4205) PDF downloads(547) Cited by(3)

Article outline

Figures and Tables

Figures(5)

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog