Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 500

The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.

Mechanism of Oxidative Stress and Synapse Dysfunction in the Pathogenesis of Alzheimer’s Disease: Understanding the Therapeutics Strategies

Open access
Kamat, Pradip K., Kalani, Anuradha, Rai, Shivika, Swarnkar, Supriya, Tota, Santoshkumar, Nath, Chandishwar, Tyagi, Neetu·2016·Molecular Neurobiology
DOI 10.1007/s12035-014-9053-6
Open this paper in CoChat — free account

Abstract

Synapses are formed by interneuronal connections that permit a neuronal cell to pass an electrical or chemical signal to another cell. This passage usually gets damaged or lost in most of the neurodegenerative diseases. It is widely believed that the synaptic dysfunction and synapse loss contribute to the cognitive deficits in patients with Alzheimer’s disease (AD). Although pathological hallmarks of AD are senile plaques, neurofibrillary tangles, and neuronal degeneration which are associated with increased oxidative stress, synaptic loss is an early event in the pathogenesis of AD. The involvement of major kinases such as mitogen-activated protein kinase (MAPK), extracellular receptor kinase (ERK), calmodulin-dependent protein kinase (CaMKII), glycogen synthase-3β (GSK-3β), cAMP response element-binding protein (CREB), and calcineurin is dynamically associated with oxidative stress-mediated abnormal hyperphosphorylation of tau and suggests that alteration of these kinases could exclusively be involved in the pathogenesis of AD. N-methyl-d-aspartate (NMDA) receptor (NMDAR) activation and beta amyloid (Aβ) toxicity alter the synapse function, which is also associated with protein phosphatase (PP) inhibition and tau hyperphosphorylation (two main events of AD). However, the involvement of oxidative stress in synapse dysfunction is poorly understood. Oxidative stress and free radical generation in the brain along with excitotoxicity leads to neuronal cell death. It is inferred from several studies that excitotoxicity, free radical generation, and altered synaptic function encouraged by oxidative stress are associated with AD pathology. NMDARs maintain neuronal excitability, Ca2+ influx, and memory formation through mechanisms of synaptic plasticity. Recently, we have reported the mechanism of the synapse redox stress associated with NMDARs altered expression. We suggest that oxidative stress mediated through NMDAR and their interaction with other molecules might be a driving force for tau hyperphosphorylation and synapse dysfunction. Thus, understanding the oxidative stress mechanism and degenerating synapses is crucial for the development of therapeutic strategies designed to prevent AD pathogenesis.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s12035-014-9053-6

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 31 references

Research works printed but not linked: 131

  1. Wang Z, Yang L, Zheng H (2012) Role of APP and Abeta in synaptic physiology. Curr Alzheimer Res 9:217–226 · DOI
  2. Bezprozvanny I, Mattson MP (2008) Neuronal calcium mishandling and the pathogenesis of Alzheimer’s disease. Trends Neurosci 31:454–463 · DOI · Paper page
  3. Rai S, Kamat PK, Nath C, Shukla R (2014) Glial activation and post-synaptic neurotoxicity: the key events in streptozotocin (ICV) induced memory impairment in rats. Pharmacol Biochem Behav 117:104–117 · DOI
  4. Kamat PK, Tota S, Shukla R, Ali S, Najmi AK, Nath C (2012) Mitochondrial dysfunction: a crucial event in okadaic acid (ICV) induced memory impairment and apoptotic cell death in rat brain. Pharmacol Biochem Behav 100:311–319 · DOI
  5. Kamat PK, Rai S, Swarnkar S, Shukla R, Nath C (2014) Mechanism of synapse redox stress in okadaic acid (ICV) induced memory impairment: role of NMDA receptor. Neurochem Int. doi: 10.1016/j.neuint.2014.06.012 · DOI
  6. Rai S, Kamat PK, Nath C, Shukla R (2013) A study on neuroinflammation and NMDA receptor function in STZ (ICV) induced memory impaired rats. J Neuroimmunol 254:1–9 · DOI
  7. Kamat PK, Rai S, Swarnkar S, Shukla R, Ali S, Najmi AK, Nath C (2013) Okadaic acid-induced tau phosphorylation in rat brain: role of NMDA receptor. Neuroscience 238:97–113 · DOI
  8. Nicholls DG (2002) Mitochondrial function and dysfunction in the cell: its relevance to aging and aging-related disease. Int J Biochem Cell Biol 34:1372–1381 · DOI · Paper page
  9. Farooqui AA, Yi Ong W, Lu XR, Halliwell B, Horrocks LA (2001) Neurochemical consequences of kainate-induced toxicity in brain: involvement of arachidonic acid release and prevention of toxicity by phospholipase A(2) inhibitors. Brain Res Brain Res Rev 38:61–78 · DOI
  10. Bell KF, Bennett DA, Cuello AC (2007) Paradoxical upregulation of glutamatergic presynaptic boutons during mild cognitive impairment. J Neurosci 27:10810–10817 · DOI
  11. Fetterolf F, Foster KA (2011) Regulation of long-term plasticity induction by the channel and C-terminal domains of GluN2 subunits. Mol Neurobiol 44:71–82 · DOI
  12. Kamat PK, Tota S, Saxena G, Shukla R, Nath C (2010) Okadaic acid (ICV) induced memory impairment in rats: a suitable experimental model to test anti-dementia activity. Brain Res 1309:66–74 · DOI
  13. Droge W (2002) Aging-related changes in the thiol/disulfide redox state: implications for the use of thiol antioxidants. Exp Gerontol 37:1333–1345 · DOI · Paper page
  14. Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95 · DOI · Paper page
  15. Kissova I, Plamondon LT, Brisson L, Priault M, Renouf V, Schaeffer J, Camougrand N, Manon S (2006) Evaluation of the roles of apoptosis, autophagy, and mitophagy in the loss of plating efficiency induced by Bax expression in yeast. J Biol Chem 281:36187–36197 · DOI
  16. Prast H, Philippu A (2001) Nitric oxide as modulator of neuronal function. Prog Neurobiol 64:51–68 · DOI · Paper page
  17. Liu D, Liu J, Sun D, Alcock NW, Wen J (2003) Spinal cord injury increases iron levels: catalytic production of hydroxyl radicals. Free Radic Biol Med 3:64–71 · DOI
  18. Sachdeva R, Babbar R, Puri V, Agarwal S, Krishana B (2011) Correlation between cognitive functions and nitric oxide levels in patients with dementia. Clin EEG Neurosci 42:190–194 · DOI
  19. Chopra K, Misra S, Kuhad A (2011) Neurobiological aspects of Alzheimer’s disease. Expert Opin Ther Targets 15:535–555 · DOI
  20. Shin JH, Linden DJ (2005) An NMDA receptor/nitric oxide cascade is involved in cerebellar LTD but is not localized to the parallel fiber terminal. J Neurophysiol 94:4281–4289 · DOI
  21. Nicholls DG, Johnson-Cadwell L, Vesce S, Jekabsons M, Yadava N (2007) Bioenergetics of mitochondria in cultured neurons and their role in glutamate excitotoxicity. J Neurosci Res 85:3206–3212 · DOI · Paper page
  22. Loh KP, Huang SH, De Silva R, Tan BK, Zhu YZ (2006) Oxidative stress: apoptosis in neuronal injury. Curr Alzheimer Res 3:327–337 · DOI · Paper page
  23. Engidawork E, Gulesserian T, Yoo BC, Cairns N, Lubec G (2001) Alteration of caspases and apoptosis-related proteins in brains of patients with Alzheimer’s disease. Biochem Biophys Res Commun 281:84–93 · DOI
  24. Glazner GW, Chan SL, Lu C, Mattson MP (2000) Caspase-mediated degradation of AMPA receptor subunits: a mechanism for preventing excitotoxic necrosis and ensuring apoptosis. J Neurosci 20:3641–3649 · DOI
  25. Sastry PS, Rao KS (2000) Apoptosis and the nervous system. J Neurochem 74:1–20 · DOI · Paper page
  26. Mattson MP, Duan W (1999) “Apoptotic” biochemical cascades in synaptic compartments: roles in adaptive plasticity and neurodegenerative disorders. J Neurosci Res 58:152–166 · doi:10.1002/(sici)1097-4547(19991001)58:1<152::aid-jnr15>3.0.co;2-v
  27. Louneva N, Cohen JW, Han LY, Talbot K, Wilson RS, Bennett DA, Trojanowski JQ, Arnold SE (2008) Caspase-3 is enriched in postsynaptic densities and increased in Alzheimer’s disease. Am J Pathol 173:1488–1495 · DOI · Paper page
  28. Jo J, Whitcomb DJ, Olsen KM, Kerrigan TL, Lo SC, Bru-Mercier G, Dickinson B, Scullion S, Sheng M, Collingridge G, Cho K (2011) Abeta(1-42) inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3beta. Nat Neurosci 14:545–547 · DOI · Paper page
  29. Yamaguchi R, Perkins G (2009) Dynamics of mitochondrial structure during apoptosis and the enigma of Opa1. Biochim Biophys Acta 1787:963–972 · DOI
  30. Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PL, Jones PK, Petersen RB, Perry G, Smith MA (2001) Mitochondrial abnormalities in Alzheimer’s disease. J Neurosci 21:3017–3023 · DOI · Paper page
  31. Cardoso SM, Rego AC, Penacho N, Oliveira CR (2004) Apoptotic cell death induced by hydrogen peroxide in NT2 parental and mitochondrial DNA depleted cells. Neurochem Int 45:693–698 · DOI
  32. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84 · DOI · Paper page
  33. Zhang YQ, Herman B (2008) Expression and modification of ARC (apoptosis repressor with a CARD domain) is distinctly regulated by oxidative stress in cancer cells. J Cell Biochem 104:818–825 · DOI
  34. Zhang XD, Wang Y, Wu JC, Lin F, Han R, Han F, Fukunaga K, Qin ZH (2009) Down-regulation of Bcl-2 enhances autophagy activation and cell death induced by mitochondrial dysfunction in rat striatum. J Neurosci Res 87:3600–3610 · DOI
  35. Moreira PI, Zhu X, Wang X, Lee HG, Nunomura A, Petersen RB, Perry G, Smith MA (2009) Mitochondria: a therapeutic target in neurodegeneration. Biochim Biophys Acta 1802:212–220 · DOI · Paper page
  36. Cui H, Chen B, Chicoine LG, Nelin LD (2011) Overexpression of cationic amino acid transporter-1 increases nitric oxide production in hypoxic human pulmonary microvascular endothelial cells. Clin Exp Pharmacol Physiol 38:796–803 · DOI
  37. Dumont M, Stack C, Elipenahli C, Jainuddin S, Gerges M, Starkova NN, Yang L, Starkov AA, Beal F (2011) Behavioral deficit, oxidative stress, and mitochondrial dysfunction precede tau pathology in P301S transgenic mice. FASEB J 25:4063–4072 · DOI
  38. Ho AK, Terriff DL, Price DM, Wloka MT, Chik CL (2007) The role of inducible repressor proteins in the adrenergic induction of arylalkylamine-N-acetyltransferase and mitogen-activated protein kinase phosphatase-1 in rat pinealocytes. Endocrinology 148:743–751 · DOI
  39. Li X, Schulz E, Wenzel P, Munzel T, Daiber A (2014) Mitochondrial redox signaling: interaction of mitochondrial reactive oxygen species with other sources of oxidative stress. Antioxid Redox Signal 20:308–324 · DOI · Paper page
  40. Bhandari A, Holmes CP, Szardenings AK (2004) Alpha, alpha-difluoro-beta-ketophosphonates as potent inhibitors of protein tyrosine phosphatase 1B. Bioorg Med Chem Lett 14:4301–4306 · doi:10.1016/j.bmcl.2004.05.082
  41. Tibbles LA, Woodgett JR (1999) The stress-activated protein kinase pathways. Cell Mol Life Sci 55:1230–1254 · DOI · Paper page
  42. Fuentes F, Zimmer D, Atienza M, Schottenfeld J, Penkala I, Bale T, Bence KK, Arregui CO (2012) Protein tyrosine phosphatase PTP1B is involved in hippocampal synapse formation and learning. PLoS ONE 7:e41536 · DOI
  43. Evans DB, Rank KB, Bhattacharya K, Thomsen DR, Gurney ME, Sharma SK (2000) Tau phosphorylation at serine 396 and serine 404 by human recombinant tau protein kinase II inhibits tau’s ability to promote microtubule assembly. J Biol Chem 275:24977–24983 · DOI
  44. Ivanov A, Pellegrino C, Rama S, Dumalska I, Salyha Y, Ben-Ari Y, Medina I (2006) Opposing role of synaptic and extrasynaptic NMDA receptors in regulation of the extracellular signal-regulated kinases (ERK) activity in cultured rat hippocampal neurons. J Physiol 572:789–798 · DOI · Paper page
  45. Leveille F, El Gaamouch F, Gouix E, Lecocq M, Lobner D, Nicole O, Buisson A (2008) Neuronal viability is controlled by a functional relation between synaptic and extrasynaptic NMDA receptors. FASEB J 22:4258–4271 · DOI · Paper page
  46. Kaufman AM, Milnerwood AJ, Sepers MD, Coquinco A, She K, Wang L, Lee H, Craig AM, Cynader M, Raymond LA (2012) Opposing roles of synaptic and extrasynaptic NMDA receptor signaling in cocultured striatal and cortical neurons. J Neurosci 32:3992–4003 · DOI
  47. Zhou Q, Sheng M (2013) NMDA receptors in nervous system diseases. Neuropharmacology 74:69–75 · DOI · Paper page
  48. Ramirez M, Lamas M (2009) NMDA receptor mediates proliferation and CREB phosphorylation in postnatal Muller glia-derived retinal progenitors. Mol Vis 15:713–721
  49. Gomperts SN, Carroll R, Malenka RC, Nicoll RA (2000) Distinct roles for ionotropic and metabotropic glutamate receptors in the maturation of excitatory synapses. J Neurosci 20:2229–2237 · DOI
  50. Bellone C, Nicoll RA (2007) Rapid bidirectional switching of synaptic NMDA receptors. Neuron 55:779–785 · DOI · Paper page
  51. Wang Q, Rowan MJ, Anwyl R (2004) Beta-amyloid-mediated inhibition of NMDA receptor-dependent long-term potentiation induction involves activation of microglia and stimulation of inducible nitric oxide synthase and superoxide. J Neurosci 24:6049–6056 · DOI · Paper page
  52. Kumar A, Foster TC (2004) Enhanced long-term potentiation during aging is masked by processes involving intracellular calcium stores. J Neurophysiol 91:2437–2444 · DOI
  53. Reese LC, Zhang W, Dineley KT, Kayed R, Taglialatela G (2008) Selective induction of calcineurin activity and signaling by oligomeric amyloid beta. Aging Cell 7:824–835 · DOI
  54. Phiel CJ, Wilson CA, Lee VM, Klein PS (2003) GSK-3alpha regulates production of Alzheimer’s disease amyloid-beta peptides. Nature 423:435–439 · DOI · Paper page
  55. Hansen T, Rehfeld JF, Nielsen FC (2004) GSK-3beta reduces cAMP-induced cholecystokinin gene expression by inhibiting CREB binding. Neuroreport 15:841–845 · DOI
  56. Koivisto L, Hakkinen L, Matsumoto K, McCulloch CA, Yamada KM, Larjava H (2004) Glycogen synthase kinase-3 regulates cytoskeleton and translocation of Rac1 in long cellular extensions of human keratinocytes. Exp Cell Res 293:68–80 · DOI
  57. Peineau S, Taghibiglou C, Bradley C, Wong TP, Liu L, Lu J, Lo E, Wu D, Saule E, Bouschet T, Matthews P, Isaac JT, Bortolotto ZA, Wang YT, Collingridge GL (2007) LTP inhibits LTD in the hippocampus via regulation of GSK3beta. Neuron 53:703–717 · DOI · Paper page
  58. Kim WY, Wang X, Wu Y, Doble BW, Patel S, Woodgett JR, Snider WD (2009) GSK-3 is a master regulator of neural progenitor homeostasis. Nat Neurosci 12:1390–1397 · DOI · Paper page
  59. Liu GP, Zhang Y, Yao XQ, Zhang CE, Fang J, Wang Q, Wang JZ (2008) Activation of glycogen synthase kinase-3 inhibits protein phosphatase-2A and the underlying mechanisms. Neurobiol Aging 29:1348–1358 · DOI
  60. Hetman M, Cavanaugh JE, Kimelman D, Xia Z (2000) Role of glycogen synthase kinase-3beta in neuronal apoptosis induced by trophic withdrawal. J Neurosci 20:2567–2574 · DOI · Paper page
  61. Rojo AI, Sagarra MR, Cuadrado A (2008) GSK-3beta down-regulates the transcription factor Nrf2 after oxidant damage: relevance to exposure of neuronal cells to oxidative stress. J Neurochem 105:192–202 · DOI · Paper page
  62. Jouvenceau A, Dutar P (2006) A role for the protein phosphatase 2B in altered hippocampal synaptic plasticity in the aged rat. J Physiol Paris 99:154–161 · DOI
  63. Kamsler A, Segal M (2004) Hydrogen peroxide as a diffusible signal molecule in synaptic plasticity. Mol Neurobiol 29:167–178 · DOI
  64. Lin CH, Yeh SH, Leu TH, Chang WC, Wang ST, Gean PW (2003) Identification of calcineurin as a key signal in the extinction of fear memory. J Neurosci 23:1574–1579 · DOI · Paper page
  65. Serrano F, Klann E (2004) Reactive oxygen species and synaptic plasticity in the aging hippocampus. Ageing Res Rev 3:431–443 · DOI · Paper page
  66. Chen QS, Wei WZ, Shimahara T, Xie CW (2002) Alzheimer amyloid beta-peptide inhibits the late phase of long-term potentiation through calcineurin-dependent mechanisms in the hippocampal dentate gyrus. Neurobiol Learn Mem 77:354–371 · DOI · Paper page
  67. Ermak G, Morgan TE, Davies KJ (2001) Chronic overexpression of the calcineurin inhibitory gene DSCR1 (Adapt78) is associated with Alzheimer’s disease. J Biol Chem 276:38787–38794 · DOI · Paper page
  68. Cook CN, Hejna MJ, Magnuson DJ, Lee JM (2005) Expression of calcipressin1, an inhibitor of the phosphatase calcineurin, is altered with aging and Alzheimer’s disease. J Alzheimers Dis 8:63–73 · DOI
  69. Koss DJ, Hindley KP, Riedel G, Platt B (2007) Modulation of hippocampal calcium signalling and plasticity by serine/threonine protein phosphatases. J Neurochem 102:1009–1023 · DOI
  70. Lu Y, Rosenberg PA (2007) NMDA receptor-mediated extracellular adenosine accumulation is blocked by phosphatase 1/2A inhibitors. Brain Res 1155:116–124 · DOI
  71. Butterfield DA, Pocernich CB (2003) The glutamatergic system and Alzheimer’s disease: therapeutic implications. CNS Drugs 17:641–652 · DOI · Paper page
  72. Li YY, Cui JG, Hill JM, Bhattacharjee S, Zhao Y and Lukiw WJ (2011) Increased expression of miRNA-146a in Alzheimer’s disease transgenic mouse models. Neurosci Lett 487:94–98. · DOI · Paper page
  73. McKinney RA (2010) Excitatory amino acid involvement in dendritic spine formation, maintenance and remodelling. J Physiol 588:107–116 · DOI
  74. Mondragon-Rodriguez S, Trillaud-Doppia E, Dudilot A, Bourgeois C, Lauzon M, Leclerc N, Boehm J (2012) Interaction of endogenous tau protein with synaptic proteins is regulated by N-methyl-D-aspartate receptor-dependent tau phosphorylation. J Biol Chem 287:32040–32053 · DOI · Paper page
  75. Moreno H, Choi S, Yu E, Brusco J, Avila J, Moreira JE, Sugimori M, Llinas RR (2011) Blocking effects of human tau on squid giant synapse transmission and its prevention by T-817 MA. Front Synaptic Neurosci 3:3 · DOI
  76. Ittner LM, Gotz J (2011) Amyloid-beta and tau—a toxic pas de deux in Alzheimer’s disease. Nat Rev Neurosci 12:65–72 · DOI · Paper page
  77. Zhang L, Li YH, Meng K, Xie W (2010) The expressions of AMPAR/GluR2 in hippocampal CA1 area of rats before and after late-phase long-term potentiation reversal. Sheng Li Xue Bao 62:23–29
  78. Zhang H, Wu CY, Wang W, Harrington MA (2011) Interneuronal synapses formed by motor neurons appear to be glutamatergic. Neuroreport 22:809–813 · doi:10.1097/wnr.0b013e32834b6d5c
  79. Massey PV, Johnson BE, Moult PR, Auberson YP, Brown MW, Molnar E, Collingridge GL, Bashir ZI (2004) Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression. J Neurosci 24:7821–7828 · DOI · Paper page
  80. Perez-Otano I, Ehlers MD (2004) Learning from NMDA receptor trafficking: clues to the development and maturation of glutamatergic synapses. Neurosignals 13:175–189 · DOI
  81. Desilva TM, Kinney HC, Borenstein NS, Trachtenberg FL, Irwin N, Volpe JJ, Rosenberg PA (2007) The glutamate transporter EAAT2 is transiently expressed in developing human cerebral white matter. J Comp Neurol 501:879–890 · DOI
  82. Ascher P, Nowak L (2009) Early biophysics of the NMDA receptor channel. J Physiol 587:4563–4564 · DOI
  83. Bleich S, Sperling W, Wiltfang J, Maler JM, Kornhuber J (2003) Excitatory neurotransmission in alcoholism. Fortschr Neurol Psychiatr 71:S36–S44 · doi:10.1055/s-2003-40504
  84. Adams JP, Sweatt JD (2002) Molecular psychology: roles for the ERK MAP kinase cascade in memory. Annu Rev Pharmacol Toxicol 42:135–163 · DOI · Paper page
  85. Foster TC, Kumar A (2002) Calcium dysregulation in the aging brain. Neuroscientist 8:297–301 · DOI
  86. Hsieh H, Boehm J, Sato C, Iwatsubo T, Tomita T, Sisodia S, Malinow R (2006) AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron 52:831–843 · DOI · Paper page
  87. Vierci G, Oliveira CS, Perera LR, Bornia N, Leal RB, Rossi FM (2013) CREB is modulated in the mouse superior colliculus in developmental and experimentally-induced models of plasticity. Int J Dev Neurosci 31:46–52 · DOI
  88. Bito H, Deisseroth K, Tsien RW (1996) CREB phosphorylation and dephosphorylation: a Ca(2+)- and stimulus duration-dependent switch for hippocampal gene expression. Cell 87:1203–1214 · DOI · Paper page
  89. Hardingham GE, Chawla S, Johnson CM, Bading H (1997) Distinct functions of nuclear and cytoplasmic calcium in the control of gene expression. Nature 385:260–265 · DOI · Paper page
  90. Vitolo OV, Sant’Angelo A, Costanzo V, Battaglia F, Arancio O, Shelanski M (2002) Amyloid beta-peptide inhibition of the PKA/CREB pathway and long-term potentiation: reversibility by drugs that enhance cAMP signaling. Proc Natl Acad Sci U S A 99:13217–13221 · DOI · Paper page
  91. Li XY, Zhan XR, Liu XM, Wang XC (2011) CREB is a regulatory target for the protein kinase Akt/PKB in the differentiation of pancreatic ductal cells into islet beta-cells mediated by hepatocyte growth factor. Biochem Biophys Res Commun 404:711–716 · DOI
  92. Arlt S, Müller-Thomsen TM, Beisiegel U, Kontush A (2012) Effect of one-year vitamin C- and E-supplementation on cerebrospinal fluid oxidation parameters and clinical course in Alzheimer’s disease. Neurochem Res 37:2706–2714 · DOI
  93. Bagi Z, Cseko C, Toth E, Koller A (2003) Oxidative stress-induced dysregulation of arteriolar wall shear stress and blood pressure in hyperhomocysteinemia is prevented by chronic vitamin C treatment. Am J Physiol Heart Circ Physiol 285:2277–2283 · DOI
  94. Nadeau A, Roberge AG (1988) Effects of vitamin B12 supplementation on choline acetyltransferase activity in cat brain. Int J Vitam Nutr Res 58:402–406
  95. Ikeda T, Yamamoto K, Takahashi K (1992) Treatment of Alzheimer-type dementia with intravenous methylcobalamin. Clin Ther 14:426–437
  96. Sung S, Yao Y, Uryu K et al (2004) Early vitamin E supplementation in young but not aged mice reduces Abeta levels and amyloid deposition in a transgenic model of Alzheimer’s disease. FASEB J 18:323–325 · DOI · Paper page
  97. Nakashima H, Ishihara T, Yokota O et al (2004) Effects of α-tocopherol on an animal model of tauopathies. Free Radic Biol Med 37:176–186 · DOI
  98. Pavlik VN, Doody RS, Rountree SD, Darby EJ (2009) Vitamin E use is associated with improved survival in an Alzheimer’s disease cohort. Dement Geriatr Cogn Disord 28:536–540 · DOI
  99. Bolognesi ML, Bergamini C, Fato R, Oiry J, Vasseur JJ, Smietana M (2014) Synthesis of new lipoic acid conjugates and evaluation of their free radical scavenging and neuroprotective activities. Chem Biol Drug Des 83:688–696 · DOI
  100. Sancheti H, Kanamori K, Patil I, Díaz Brinton R, Ross BD, Cadenas E (2014) Reversal of metabolic deficits by lipoic acid in a triple transgenic mouse model of Alzheimer’s disease: a 13C NMR study. J Cereb Blood Flow Metab 34:288–296 · DOI
  101. Kryscio RJ, Abner EL, Schmitt FA et al (2013) A randomized controlled Alzheimer’s disease prevention trial’s evolution into an exposure trial: the PREADViSE trial. J Nutr Health Aging 17:72–75 · doi:10.1007/s12603-013-0004-0
  102. Rajasekar N, Dwivedi S, Tota SK, Kamat PK, Hanif K, Nath C, Shukla R (2013) Neuroprotective effect of curcumin on okadaic acid induced memory impairment in mice. Eur J Pharmacol 715:381–394 · DOI
  103. Ringman M, Cole GM, Tend E (2008) Oral curcumin for the treatment of mild-to-moderate Alzheimer’s disease: tolerability and clinical and biomarker efficacy results of a placebo-controlled 24-week study. Proceedings of the International Conference of Alzheimer’s disease Chicago, abstract. · DOI
  104. Remington R, Chan A, Paskavitz J, Shea TB (2009) Efficacy of a vitamin/nutriceutical formulation for moderate-stage to later-stage Alzheimer’s disease: a placebo-controlled pilot study. Am J Alzheimers Dis Other Demen 24:27–33 · DOI
  105. Chan A, Remington R, Kotyla E, Lepore A, Zemianek J, Shea TB (2010) A vitamin/nutriceutical formulation improves memory and cognitive performance in community-dwelling adults without dementia. J Nutr Health Aging 14:224–230 · DOI
  106. Thal LJ, Grundman M, Berg J, Ernstrom K, Margolin R, Pfeiffer E, Weiner MFF, Zamrini E, Thomas RG (2003) Idebenone treatment fails to slow cognitive decline in Alzheimer’s disease. Neurology 61:1498–1502 · DOI · Paper page
  107. Mulnard RA, Cotman CW, Kawas C et al (2000) Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. J Am Med Assoc 283:1007–1015 · DOI · Paper page
  108. Singh S, Thakur MK (2011) Gonadal steroids do not affect apolipoprotein E expression in aging mouse cerebral cortex. Cell Mol Neurobiol 31:401–405 · DOI
  109. Boldogh I, Liebenthal D, Hughes TK et al (2003) Modulation of 4HNE-mediated signaling by proline-rich peptides from ovine colostrum. J Mol Neurosci 20:125–134 · DOI
  110. Zabłocka A, Janusz M (2012) Effect of the proline-rich polypeptide complex/colostrininTM on the enzymatic antioxidant system. Arch Immunol Ther Exp 60:383–390 · DOI
  111. Leszek J, Inglot AD, Janusz M et al (2002) Colostrinin proline-rich polypeptide complex fromovine colostrum—a long-term study of its efficacy in Alzheimer’s disease. Med Sci Monit 8:I93–I96
  112. Bilikiewicz A, Gaus W (2004) Colostrinin1 (a naturally occurring proline-rich, polypeptide mixture) in the treatment of Alzheimer’s disease. J Alzheimers Dis 6:17–26 · DOI
  113. Jia N, Han K, Kong JJ, Zhang XM, Sha S, Ren GR, Cao YP (2013) (−)-Epigallocatechin-3-gallate alleviates spatial memory impairment in APP/PS1 mice by restoring IRS-1 signaling defects in the hippocampus. Mol Cell Biochem 380:211–218 · DOI
  114. Li SY, Wang XB, Kong LY (2014) Design, synthesis and biological evaluation of imine resveratrol derivatives as multi-targeted agents against Alzheimer’s disease. Eur J Med Chem 71:36–45 · DOI
  115. Lu C, Guo Y, Yan J, Luo Z, Luo HB, Yan M, Huang L, Li X (2013) Design, synthesis, and evaluation of multitarget-directed resveratrol derivatives for the treatment of Alzheimer’s disease. J Med Chem 56:5843–5859 · DOI · Paper page
  116. Jones RW (2010) Dimebon disappointment. Alzheimers Res Ther 2:25 · DOI
  117. Steele JW, Gandy S (2013) Latrepirdine (Dimebon®), a potential Alzheimer therapeutic, regulates autophagy and neuropathology in an Alzheimer mouse model. Autophagy 9:617–818 · DOI
  118. Bharadwaj PR, Bates KA, Porter T, Teimouri E, Perry G, Steele JW, Gandy S, Groth D, Martins RN, Verdile G (2013) Latrepirdine: molecular mechanisms underlying potential therapeutic roles in Alzheimer’s and other neurodegenerative diseases. Transl Psychiatry 3:e332 · DOI
  119. Quinn JF, Bussiere JR, Hammond RS et al (2007) Chronic dietary α-lipoic acid reduces deficits in hippocampal memory of aged Tg2576 mice. Neurobiol Aging 28:213–225 · DOI · Paper page
  120. Lu P, Mamiya T, Lu LL et al (2009) Silibinin prevents amyloid b peptide-induced memory impairment and oxidative stress in mice. Br J Pharmacol 157:1270–1277 · DOI · Paper page
  121. Tota S, Kamat PK, Shukla R, Nath C (2011) Improvement of brain energy metabolism and cholinergic functions contributes to the beneficial effects of silibinin against streptozotocin induced memory impairment. Behav Brain Res 221:207–215 · DOI
  122. Tota S, Awasthi H, Kamat PK, Nath C, Hanif K (2010) Protective effect of quercetin against intracerebral streptozotocin induced reduction in cerebral blood flow and impairment of memory in mice. Behav Brain Res 209:73–79 · DOI
  123. Feng Z, Zhang JT (2004) Protective effect of melatonin on β-amyloid-induced apoptosis in rat astroglioma c6 cells and its mechanism. Free Radic Biol Med 37:1790–1801 · DOI
  124. Matsubara E, Bryant-Thomas T, Quinto JP et al (2003) Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer’s disease. J Neurochem 85:1101–1108 · DOI · Paper page
  125. Saxena G, Bharti S, Kamat PK, Sharma S, Nath C (2010) Melatonin alleviates memory deficits and neuronal degeneration induced by intracerebroventricular administration of streptozotocin in rats. Pharmacol Biochem Behav 94:397–403 · doi:10.1016/j.pbb.2009.09.022
  126. Prasanthi JRP, Dasari B, Marwarha G et al (2010) Caffeine protects against oxidative stress and Alzheimer’s disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet. Free Radic Biol Med 49:1212–1220 · DOI · Paper page
  127. Andrieu S, Ousset PJ, Coley N, Ouzid M, Mathiex-Fortunet H, Vellas B, The GuidAge study Group (2008) GuidAge study: a 5-year double-blind, randomized trial of EGb761 for the prevention of Alzheimer’s disease in elderly subjects with memory complaints rationale, design and baseline data. Curr Alzheimer Res 5:406–415 · DOI
  128. Vellas B, Coley N, Ousset PJ et al (2012) Long-term use of standardized ginkgo biloba extract for the prevention of Alzheimer’ disease (GuidAge): a randomised placebo-controlled trial. Lancet Neurol 11:851–859 · DOI · Paper page
  129. Snitz BE, O’Meara ES, Carlson MC, Arnold AM, Ives DG, Rapp SR, Saxton J, Lopez OL, Dunn LO, Sink KM, DeKosky ST, Ginkgo Evaluation of Memory (GEM) Study Investigators (2009) Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial. JAMA 302:2663–2670 · DOI · Paper page
  130. Saxena G, Singh SP, Pal R, Singh S, Pratap R, Nath C (2007) Gugulipid, an extract of Commiphora whighitii with lipid-lowering properties, has protective effects against streptozotocin-induced memory deficits in mice. Pharmacol Biochem Behav 86:797–805 · DOI
  131. Niranjan R, Kamat PK, Nath C, Shukla R (2010) Evaluation of guggulipid and nimesulide on production of inflammatory mediators and GFAP expression in LPS stimulated rat astrocytoma, cell line (C6). J Ethnopharmacol 127:625–630 · doi:10.1016/j.jep.2009.12.012

Cited by

See all 500

Metadata

Authors
Kamat, P. K., Kalani, A., Rai, S., Swarnkar, S., Tota, S., Nath, C., & Tyagi, N.
Venue
Molecular Neurobiology
Publisher
Springer Science and Business Media LLC
Published
2014-12-17
Volume
53
Issue
1
Pages
648-661
ISSN
  • 0893-7648 (ISSN-L)
  • 1559-1182
DOI
10.1007/s12035-014-9053-6
OpenAlex
W1968602836
Cited by
500
References
31
FWCI
7.00
Type
journal article
Language
en
Open access
green
Licence
www.springer.com/tdm (tdm)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Mechanism of Oxidative Stress and Synapse Dysfunction in the Pathogenesis of Alzheimer’s Disease: Understanding the Therapeutics Strategies. https://app.cochat.ai/papers/10.1007/s12035-014-9053-6
The paper
Kamat, P. K., Kalani, A., Rai, S., Swarnkar, S., Tota, S., Nath, C., & Tyagi, N. (2016). Mechanism of Oxidative Stress and Synapse Dysfunction in the Pathogenesis of Alzheimer’s Disease: Understanding the Therapeutics Strategies. Molecular Neurobiology. https://doi.org/10.1007/s12035-014-9053-6

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.