Abstract
Alzheimer's disease (AD) is the most common neurodegenerative disorder, and its pathogenesis is likely to be associated with multiple etiologies and mechanisms in which oxidative stress and deficits of neurotransmitter receptors may play important roles. It has been indicated that a high level of free radicals can influence the expressions of nicotinic receptors (nAChRs), muscarinic receptors (mAChRs), and N-methyl-D-aspartate (NMDA) receptors, exhibiting disturbances of cellular membrane by lipid peroxidation, damages of the protein receptors by protein oxidation, and possible modified gene expressions of these receptors by DNA oxidation. nAChRs have shown an antioxidative effect by a direct or an indirect pathway; mAChR stimulation may generate reactive oxygen species, which might be a physiological compensative reaction, or improve oxidative stress; and high stimulation to NMDA receptors can increase the sensitivity of oxidative stress of neurons. This review may provide complemental information for understanding the correlation between oxidative stress and changed cholinergic and glutaminergic receptors in AD processing, and for revealing the underlying molecular mechanisms of these factors in the multiple etiologies and pathophysiology of the disorder.
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References
Selkoe DJ . Alzheimer's disease is a synaptic failure. Science 2002; 298: 789–91.
Sorrentino G, Bonavita V . Neurodegeneration and Alzheimer's disease: the lesson from tauopathies. Neurol Sci 2007; 28: 63–71.
Blennow K, de Leon MJ, Zetterberg H . Alzheimer's disease. Lancet 2006; 368: 387–403.
Tariot PN, Federoff HJ . Current treatment for Alzheimer's disease and future prospects. Alzheimer Dis Assoc Disord 2003; 17: S105–113.
Facchinetti F, Dawson VL, Dawson TM . Free radicals as mediators of neuronal injury. Cell Mol Neurobiol 1998; 18: 667–82.
Betteridge DJ . What is oxidative stress? Metabolism 2000; 49: 3–8.
Butterfield DA, Reed T, Newman SF, Sultana R . Roles of amyloid beta-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer's disease and mild cognitive impairment. Free Radic Biol Med 2007; 43: 658–77.
Christen Y . Oxidative stress and Alzheimer disease. Am J Clin Nutr 2000; 71: S621–629.
Smith MA, Perry G, Richey PL, Sayre LM, Anderson VE, Beal MF, et al. Oxidative damage in Alzheimer's. Nature 1996; 382: 120–1.
Smith MA, Hirai K, Hsiao K, Pappolla MA, Harris PL, Siedlak SL, et al. Amyloid-beta deposition in Alzheimer transgenic mice is associated with oxidative stress. J Neurochem 1998; 70: 2212–5.
Teunissen CE, de Vente J, Steinbusch HW, De Bruijn C . Biochemical markers related to Alzheimer's dementia in serum and cerebrospinal fluid. Neurobiol Aging 2002; 23: 485–508.
Pratico D, Uryu K, Leight S, Trojanoswki JQ, Lee VM . Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J Neurosci 2001; 21: 4183–7.
Pratico D . Alzheimer's disease and oxygen radicals: new insights. Biochem Pharmacol 2002; 63: 563–7.
Castellani RJ, Zhu X, Lee HG, Moreira PI, Perry G, Smith MA . Neuropathology and treatment of Alzheimer disease: did we lose the forest for the trees? Expert Rev Neurother 2007; 7: 473–85.
Smith MA, Rottkamp CA, Nunomura A, Raina AK, Perry G . Oxidative stress in Alzheimer's disease. Biochim Biophys Acta 2000; 1502: 139–44.
Guan Z, Wang Y, Cairns NJ, Lantos PL, Dallner G, Sindelar PJ . Decrease and structural modifications of phosphatidylethanolamine plasmalogen in the brain with Alzheimer's disease. J Neuropathol Exp Neurol 1999; 58: 740–7.
Yu WF, Nordberg A, Ravid R, Guan ZZ . Correlation of oxidative stress and the loss of the nicotinic receptor alpha 4 subunit in the temporal cortex of patients with Alzheimer's disease. Neurosci Lett 2003; 338: 13–6.
Guan ZZ, Yu WF, Shan KR, Nordman T, Olsson J, Nordberg A . Loss of nicotinic receptors induced by beta-amyloid peptides in PC12 cells: possible mechanism involving lipid peroxidation. J Neurosci Res 2003; 71: 397–406.
Smith MA, Casadesus G, Joseph JA, Perry G . Amyloid-beta and tau serve antioxidant functions in the aging and Alzheimer brain. Free Radic Biol Med 2002; 33: 1194–9.
Paterson D, Nordberg A . Neuronal nicotinic receptors in the human brain. Prog Neurobiol 2000; 61: 75–111.
Nordberg A . Nicotinic receptor abnormalities of Alzheimer's disease: therapeutic implications. Biol Psychiatry 2001; 49: 200–10.
Marutle A, Warpman U, Bogdanovic N, Lannfelt L, Nordberg A . Neuronal nicotinic receptor deficits in Alzheimer's patients with the Swedish amyloid precursor protein 670/671 mutation. J Neurochem 1999; 72: 1161–9.
Guan ZZ, Zhang X, Ravid R, Nordberg A . Decreased protein levels of nicotinic receptor subunits in the hippocampus and temporal cortex of patients with Alzheimer's disease. J Neurochem 2000; 74: 237–43.
Yu WF, Guan ZZ, Bogdanovic N, Nordberg A . High selective expression of alpha7 nicotinic receptors on astrocytes in the brains of patients with sporadic Alzheimer's disease and patients carrying Swedish APP 670/671 mutation: a possible association with neuritic plaques. Exp Neurol 2005; 192: 215–25.
Guan ZZ, Miao H, Tian JY, Unger C, Nordberg A, Zhang X . Suppressed expression of nicotinic acetylcholine receptors by nanomolar beta-amyloid peptides in PC12 cells. J Neural Transm 2001; 1417–33.
Xiu X, Nordberg A, Shan KR, Yu WF, Thordman T, Olsson JM, et al. Lovastatin stimulates up-regulation of alpha7 nicotinic receptors in cultured neurons without cholesterol dependency, a mechanism involving production of the alpha-form of secreted amyloid precursor protein. J Neurosci Res 2005; 82: 531–41.
Dineley KT, Bell KA, Bui D, Sweatt JD . Beta-Amyloid peptide activates alpha 7 nicotinic acetylcholine receptors expressed in Xenopus oocytes. J Biol Chem 2002; 277: 25056–61.
Bednar I, Paterson D, Marutle A, Pham TM, Svedberg M, Hellstrom-Lindahl E, et al. Selective nicotinic receptor consequences in APP(SWE) transgenic mice. Mol Cell Neurosci 2002; 20: 354–65.
van Koppen CJ, Kaiser B . Regulation of muscarinic acetylcho-line receptor signaling. Pharmacol Ther 2003; 98: 197–220.
Levey AI . Muscarinic acetylcholine receptor expression in memory circuits: implications for treatment of Alzheimer disease. Proc Natl Acad Sci USA 1996; 93: 13541–6.
Svensson AL, Warpman U, Hellstrom-Lindahl E, Bogdanovic N, Lannfelt L, Nordberg A . Nicotinic receptors, muscarinic receptors and choline acetyltransferase activity in the temporal cortex of Alzheimer patients with differing apolipoprotein E genotypes. Neurosci Lett 1997; 232: 37–40.
Gu Z, Zhong P, Yan Z . Activation of muscarinic receptors inhibits beta-amyloid peptide-induced signaling in cortical slices. J Biol Chem 2003; 278: 17546–56.
Genis I, Fisher A, Michaelson DM . Site-specific dephosphorylation of tau of apolipoprotein E-deficient and control mice by M1 muscarinic agonist treatment. J Neurochem 1999; 72: 206–13.
Wang SZ, Zhu SZ, Mash DC, el-Fakahany EE . Comparison of the concentration of messenger RNA encoding four muscarinic receptor subtypes in control and Alzheimer brains. Brain Res Mol Brain Res 1992; 16: 64–70.
Flynn DD, Ferrari-DiLeo G, Mash DC, Levey AI . Differential regulation of molecular subtypes of muscarinic receptors in Alzheimer's disease. J Neurochem 1995; 64: 1888–91.
Danysz W, Parsons CG . The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer's disease: preclinical evidence. Int J Geriatr Psychiatr 2003; 18: S23–32.
Dunah AW, Yasuda RP, Luo J, Wang Y, Prybylowski KL, Wolfe BB . Biochemical studies of the structure and function of the N-methyl-D-aspartate subtype of glutamate receptors. Mol Neurobiol 1999; 19: 151–79.
Francis PT, Sims NR, Procter AW, Bowen DM . Cortical pyramidal neuron loss may cause glutamatergic hypoactivity and cognitive impairment in Alzheimer's disease: investigative and therapeutic perspectives. J Neurochem 1993; 60: 1589–604.
Greenamyre JT, Penney JB, Young AB, D'Amato CJ, Hicks SP, Shoulson I . Alterations in L-glutamate binding in Alzheimer's and Huntington's diseases. Science 1985; 227: 1496–9.
Panegyres PK, Zafiris-Toufexis K, Kakulas BA . The mRNA of the NR1 subtype of glutamate receptor in Alzheimer's disease. J Neural Transm 2002; 109: 77–89.
Brorson JR, Bindokas VP, Iwama T, Marcuccilli CJ, Chisholm JC, Miller RJ . The Ca2+ influx induced by beta-amyloid peptide 25–35 in cultured hippocampal neurons results from network excitation. J Neurobiol 1995; 26: 325–38.
Guo Q, Fu W, Sopher BL, Miller MW, Ware CB, Martin GM, et al. Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in mice. Nat Med 1999; 5: 101–6.
Moechars D, Dewachter I, Lorent K, Reverse D, Baekelandt V, Naidu A, et al. Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain. J Biol Chem 1999; 274: 6483–92.
Lee HG, Zhu X, Ghanbari HA, Ogawa O, Raina AK, O'Neill MJ, et al. Differential regulation of glutamate receptors in Alzheimer's disease. Neurosignals 2002; 11: 282–92.
Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ . Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med 2003; 348: 1333–41.
Fong TM, McNamee MG . Correlation between acetylcholine receptor function and structural properties of membranes. Biochemistry 1986; 25: 830–40.
Choe M, Jackson C, Yu BP . Lipid peroxidation contributes to age-related membrane rigidity. Free Radic Biol Med 1995; 18: 977–84.
Guan ZZ, Zhang X, Mousavi M, Tian JY, Unger C, Nordberg A . Reduced expression of neuronal nicotinic acetylcholine receptors during the early stages of damage by oxidative stress in PC12 cells. J Neurosci Res 2001; 66: 551–8.
Pedersen WA, Fu W, Keller JN, Markesbery WR, Appel S, Smith RG, et al. Protein modification by the lipid peroxidation product 4-hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients. Ann Neurol 1998; 44: 819–24.
Li Y, King MA, Meyer EM . alpha7 nicotinic receptor-mediated protection against ethanol-induced oxidative stress and cytotoxicity in PC12 cells. Brain Res 2000; 861: 165–7.
Qi XL, Nordberg A, Xiu J, Guan ZZ . The consequences of reducing expression of the α7 nicotinic receptor by RNA interference and of stimulating its activity with an α7 agonist in SH-SY5Y cells indicate that this receptor plays a neuroprotective role in connection with the pathogenesis of Alzheimer's disease. Neurochem Int 2007; 51: 377–83.
Guan ZZ, Yu WF, Nordberg A . Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells. Neurochem Int 2003; 43: 243–9.
Arora RC, Hess ML . Effect of reduced oxygen intermediates on sarcolemmal muscarinic receptors from canine heart. Biochem Biophys Res Commun 1985; 130: 133–40.
Joseph JA, Fisher DR . Muscarinic receptor subtype determines vulnerability to amyloid beta toxicity in transfected cos-7 cells. J Alzheimers Dis 2003; 5: 197–208.
Fawcett JR, Bordayo EZ, Jackson K, Liu H, Peterson J, Svitak A, et al. Inactivation of the human brain muscarinic acetylcholine receptor by oxidative damage catalyzed by a low molecular weight endogenous inhibitor from Alzheimer's brain is prevented by pyrophosphate analogs, bioflavonoids and other antioxidants. Brain Res 2002; 950: 10–20.
Mangelus M, Kroyter A, Galron R, Sokolovsky M . Reactive oxygen species regulate signaling pathways induced by M1 muscarinic receptors in PC12 M1 cells. J Neurochem 2001; 76: 1701–11.
Kamata H, Hirata H . Redox regulation of cellular signalling. Cell Signal 1999; 11: 1–14.
Harris ME, Wang Y, Pedigo NW Jr, Hensley K, Butterfield DA, et al. Amyloid beta peptide (25–35) inhibits Na+-dependent glutamate uptake in rat hippocampal astrocyte cultures. J Neurochem 1996; 67: 277–86.
Jara-Prado A, Ortega-Vazquez A, Martinez-Ruano L, Rios C, Santamaria A . Homocysteine-induced brain lipid peroxidation: effects of NMDA receptor blockade, antioxidant treatment, and nitric oxide synthase inhibition. Neurotox Res 2003; 5: 237–43.
Kosenko E, Kaminski Y, Lopata O, Muravyov N, Felipo V . Blocking NMDA receptors prevents the oxidative stress induced by acute ammonia intoxication. Free Radic Biol Med 1999; 26: 1369–74.
Gasparova-Kvaltinova Z, Stolc S . Effect of antioxidants and NMDA antagonists on the density of NMDA binding sites in rat hippocampal slices exposed to hypoxia/reoxygenation. Methods Find Exp Clin Pharmacol 2003; 25: 17–25.
Ryu BR, Lee YA, Won SJ, Noh JH, Chang SY, Chung JM, et al. The novel neuroprotective action of sulfasalazine through blockade of NMDA receptors. J Pharmacol Exp Ther 2003, 305: 48–56.
Li L, Shou Y, Borowitz JL, Isom GE . Reactive oxygen species mediate pyridostigmine-induced neuronal apoptosis: involvement of muscarinic and NMDA receptors. Toxicol Appl Pharmacol 2001; 177: 17–25.
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This work was supported financially by grants from the Foundation of Ministry of Science and Technology of China (No 2004DFB02800 and 2006DFA33530), the Chinese National Natural Science Foundation (No 30460045), and the Foundation of Guizhou Province of China (No [2006] 400107, [2006] 52, and [2006] 6015).
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Guan, Zz. Cross-talk between oxidative stress and modifications of cholinergic and glutaminergic receptors in the pathogenesis of Alzheimer's disease. Acta Pharmacol Sin 29, 773–780 (2008). https://doi.org/10.1111/j.1745-7254.2008.00819.x
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DOI: https://doi.org/10.1111/j.1745-7254.2008.00819.x
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