Oxidative Stress Induces Intracellular Accumulation of Amyloid β-Protein (Aβ) in Human Neuroblastoma Cells

Misonou, Hiroaki; Morishima-Kawashima, Maho; Ihara, Yasuo

doi:10.1021/bi000169p

Cited by 304Alzheimer's disease research and treatmentsRedox biology and oxidative stressDementia and Cognitive Impairment Research

Oxidative Stress Induces Intracellular Accumulation of Amyloid β-Protein (Aβ) in Human Neuroblastoma Cells

Misonou, Hiroaki, Morishima-Kawashima, Maho, Ihara, Yasuo·2000·Biochemistry

DOI 10.1021/bi000169p

Open this paper in CoChat — free account

Abstract

Several lines of evidence suggest that enhanced oxidative stress is involved in the pathogenesis and/or progression of Alzheimer's disease (AD). Amyloid beta-protein (Abeta) that composes senile plaques, a major neuropathological hallmark of AD, is considered to have a causal role in AD. Thus, we have studied the effect of oxidative stress on Abeta metabolism within the cell. Here, we report that oxidative stress induced by H(2)O(2) (100-250 microM) caused an increase in the levels of intracellular Abeta in human neuroblastoma SH-SY5Y cells. Treatment with 200 microM H(2)O(2) caused significant decreases in the protein levels of full-length beta-amyloid precursor protein (APP) and its COOH-terminal fragment that is generated by beta-cleavage, while the gene expression of APP was not altered under these conditions. A pulse-chase experiment further showed a decrease in the half-life of this amyloidogenic COOH-terminal fragment but not in that of nonamyloidogenic counterpart in the H(2)O(2)-treated cells. These results suggest that oxidative stress promotes intracellular accumulation of Abeta through enhancing the amyloidogenic pathway.

Integrity signals

Registry

Crossref · 10.1021/bi000169p

Cites

19 of 19 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Aβ increases cellular RS, and these RS may in turn increase production of Aβ in a destructive autocatalytic cycle.
“Evidence also suggests that not only does Aβ increase cellular RS but that these RS may in turn increase production of Aβ in a destructive autocatalytic cycle (Misonou et al., 2000; Tamagno et al., 2002, 2005; Lin and Beal, 2006; Quiroz-Baez et al., 2009).”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Misonou et al., 2000
Aβ enhances production of cellular RS, and these RS contribute to Aβ toxicity.
“Aβ appears to enhance production of cellular RS, and these RS in turn may to contribute to Aβ toxicity.”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Misonou et al., 2000
Many experimental data suggest that oxidative stress and mitochondrial dysfunction induce an increase in the amyloidogenic cleavage of APP and an aberrant Aβ production.
“On the other hand, many experimental data suggest that oxidative stress and mitochondrial dysfunction induce an increase in the amyloidogenic cleavage of the APP and an aberrant Aβ production (Misonou et al., 2000; Perez Ortiz and Swerdlow, 2019).”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Misonou et al., 2000

Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays
Mosmann, T. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90303-4 · Cited by 56,104 · see citing works
Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: Evidence that an initially deposited species is Aβ42(43)
Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N., & Ihara, Y. (1994) · Neuron · doi:10.1016/0896-6273(94)90458-8 · Cited by 1,774 · see citing works
Self-citation
4‐Hydroxynonenal‐Derived Advanced Lipid Peroxidation End Products Are Increased in Alzheimer's Disease
Sayre, L., Zelasko, D. A., Harris, P. L. R., Perry, G., Salomon, R. G., & Smith, M. A. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.68052092.x · Cited by 1,032 · see citing works
An Assessment of Oxidative Damage to Proteins, Lipids, and DNA in Brain from Patients with Alzheimer's Disease
Lyras, L., Cairns, N. J., Jenner, A., Jenner, P., & Halliwell, B. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.68052061.x · Cited by 531 · see citing works
The promoter of Alzheimer's disease amyloid A4 precursor gene.
Salbaum, J. M., Weidemann, A., Lemaire, H.-G., Masters, C. L., & Beyreuther, K. T. (1988) · The EMBO Journal · doi:10.1002/j.1460-2075.1988.tb03136.x · Cited by 311 · see citing works
Detection of a Novel Intraneuronal Pool of Insoluble Amyloid β Protein that Accumulates with Time in Culture
Skovronsky, D. M., Doms, R. W., & Lee, V. M.-Y. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.4.1031 · Cited by 290 · see citing works
Cerebrospinal fluid F2‐isoprostane levels are increased in Alzheimer's disease
Montine, T., Markesbery, W., Morrow, J., & Roberts, L. (1998) · Annals of Neurology · doi:10.1002/ana.410440322 · Cited by 254 · see citing works
F<sub>4</sub> ‐ Isoprostanes as Specific Marker of Docosahexaenoic Acid Peroxidation in Alzheimer's Disease
Nourooz‐Zadeh, J., Liu, E. H. C., Yhlen, B., Änggåard, E. E., & Halliwell, B. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0720734.x · Cited by 187 · see citing works
Oxidative Stress Increases Production of β-Amyloid Precursor Protein and β-Amyloid (Aβ) in Mammalian Lenses, and Aβ Has Toxic Effects on Lens Epithelial Cells
Frederikse, P. H., Garland, D. L., Zigler, J. S., & Piatigorsky, J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.17.10169 · Cited by 184 · see citing works
Lipid Binding to Amyloid β‐Peptide Aggregates: Preferential Binding of Cholesterol as Compared with Phosphatidylcholine and Fatty Acids
Avdulov, N. A., Chochina, S. V., Igbavboa, U., Warden, C. S., Vassiliev, A. V., & Wood, W. G. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69041746.x · Cited by 180 · see citing works
Proteolytic Processing of the Alzheimer's Disease Amyloid Precursor Protein within Its Cytoplasmic Domain by Caspase-like Proteases
Weidemann, A., Paliga, K., Dürrwang, U., Reinhard, F. B. M., Schuckert, O., Evin, G. M., & Masters, C. L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.9.5823 · Cited by 173 · see citing works
Interleukin-1β and Glutamate Activate the NF-κB/Rel Binding Site from the Regulatory Region of the Amyloid Precursor Protein Gene in Primary Neuronal Cultures
Grilli, M., Goffi, F., Memo, M., & Spano, P. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.25.15002 · Cited by 144 · see citing works
Non-Fibrillar β-Amyloid Protein is Associated with Smooth Muscle Cells of Vessel Walls in Alzheimer Disease
Frackowiak, J., Żółtowska, A., & Wı́sniewski, H. M. (1994) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199411000-00011 · Cited by 128 · see citing works
Amyloid precursor protein, although partially detergent-insoluble in mouse cerebral cortex, behaves as an atypical lipid raft protein
Parkin, E. T., Turner, A. J., & Hooper, N. M. (1999) · Biochemical Journal · doi:10.1042/bj3440023 · Cited by 112 · see citing works
Expression of β-Amyloid Precursor Protein-CD3γ Chimeras to Demonstrate the Selective Generation of Amyloid β1–40and Amyloid β1–42 Peptides within Secretory and Endocytic Compartments
Soriano, S., Chyung, A. S. C., Chen, X., Stokin, G. B., Lee, V. M. ‐., & Koo, E. H. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.45.32295 · Cited by 89 · see citing works
Upregulation of amyloid precursor protein gene promoter in rat primary hippocampal neurons by phorbol ester, IL-1 and retinoic acid, but not by reactive oxygen species
Yang, Y., Quitschke, W. W., & Brewer, G. J. (1998) · Molecular Brain Research · doi:10.1016/s0169-328x(98)00164-8 · Cited by 62 · see citing works
Accumulation of Intracellular Amyloid-β Peptide (Aβ 1–40) in Mucopolysaccharidosis Brains
Ginsberg, S. D., Galvin, J. E., Lee, V. M. ‐., RORKE, L. B., Dickson, D. W., Wolfe, J. H. N., JONES, M. Z., & Trojanowski, J. Q. (1999) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199908000-00004 · Cited by 61 · see citing works
Role of Endoplasmic Reticulum, Endosomal–Lysosomal Compartments, and Microtubules in Amyloid Precursor Protein Metabolism of Human Neurons
LeBlanc, A. C., & Goodyer, C. G. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0721832.x · Cited by 39 · see citing works
Amyloid β-protein (Aβ) Accumulation in the Leptomeninges during Aging and in Alzheimer Disease
Hamano, T., Yoshimura, M., Yamazaki, T., Shinkai, Y., Yanagisawa, K., Kuriyama, M., & Ihara, Y. (1997) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199708000-00010 · Cited by 35 · see citing works

Flagged first, then by citations

Sorted by citations

Intracellular amyloid-β in Alzheimer's disease
LaFerla, F. M., Green, K. N., & Oddo, S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2168 · Cited by 1,942 · see citing works
Oxidative Damage Is the Earliest Event in Alzheimer Disease
Nunomura, A., Perry, G., Aliev, G., Hirai, K., Takeda, A., Balraj, E. K., Jones, P. K., Ghanbari, H., Wataya, T., Shimohama, S., et al. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.8.759 · Cited by 1,885 · see citing works
Copper Homeostasis and Neurodegenerative Disorders (Alzheimer's, Prion, and Parkinson's Diseases and Amyotrophic Lateral Sclerosis)
Gaggelli, E., Kozlowski, H., Valensin, D., & Valensin, G. (2006) · Chemical Reviews · doi:10.1021/cr040410w · Cited by 1,729 · see citing works
A Review: Inflammatory Process in Alzheimer's Disease, Role of Cytokines
Rubio-Perez, J. M., & Morillas-Ruiz, J. M. (2012) · The Scientific World JOURNAL · doi:10.1100/2012/756357 · Cited by 841 · see citing works
Involvement of oxidative stress in Alzheimer disease
Nunomura, A., Castellani, R. J., Zhu, X., Moreira, P. I., Perry, G., & Smith, M. A. (2006) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/01.jnen.0000228136.58062.bf · Cited by 611 · see citing works
Development of Multifunctional Molecules as Potential Therapeutic Candidates for Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis in the Last Decade
Savelieff, M. G., Nam, G., Kang, J., Lee, H. J., Lee, M., & Lim, M. H. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00138 · Cited by 603 · see citing works
Oxidative Stress and Neurodegenerative Disorders
Li, J., Wuliji, O., Li, W., Jiang, Z.-G., & Ghanbari, H. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms141224438 · Cited by 511 · see citing works
Caloric Intake and the Risk of Alzheimer Disease
Luchsinger, J. A., Tang, M., Shea, S. A., & Mayeux, R. P. (2002) · Archives of Neurology · doi:10.1001/archneur.59.8.1258 · Cited by 470 · see citing works
Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology of Alzheimer's Disease?
Mander, B. A., Winer, J. R., Jagust, W. J., & Walker, M. P. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.05.002 · Cited by 467 · see citing works
The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease
McManus, M. J., Murphy, M. P., & Franklin, J. L. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0552-11.2011 · Cited by 432 · see citing works
Antioxidant Vitamin Intake and Risk of Alzheimer Disease
Luchsinger, J. A., Tang, M.-X., Shea, S., & Mayeux, R. (2003) · Archives of Neurology · doi:10.1001/archneur.60.2.203 · Cited by 414 · see citing works
Apolipoprotein e sets the stage: response to injury triggers neuropathology
Mahley, R. W., & Huang, Y. (2012) · Neuron · doi:10.1016/j.neuron.2012.11.020 · Cited by 412 · see citing works
Oxidative stress increases expression and activity of BACE in NT2 neurons
Tamagno, E., Bardini, P., Obbili, A., Vitali, A., Borghi, R., Zaccheo, D., Pronzato, M. A., Danni, O., Smith, M. A., Perry, G., et al. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2002.0515 · Cited by 385 · see citing works
Metals and amyloid‐β in Alzheimer's disease
Maynard, C. J., Bush, A. I., Masters, C. L., Cappai, R., & Li, Q. (2005) · International Journal of Experimental Pathology · doi:10.1111/j.0959-9673.2005.00434.x · Cited by 353 · see citing works
A modified β‐amyloid hypothesis: intraneuronal accumulation of the β‐amyloid peptide – the first step of a fatal cascade
Wirths, O., Multhaup, G., & Bayer, T. A. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02737.x · Cited by 349 · see citing works
Inhibitory Activity on Amyloid-β Aggregation and Antioxidant Properties ofCrocus sativusStigmas Extract and Its Crocin Constituents
Papandreou, M. A., Kanakis, C. D., Polissiou, M. G., Efthimiopoulos, S., Cordopatis, P. A., Margarity, M., & Lamari, F. N. (2006) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf061932a · Cited by 342 · see citing works
Altered Metabolism of the Amyloid β Precursor Protein Is Associated with Mitochondrial Dysfunction in Down's Syndrome
Busciglio, J., Pelsman, A., Wong, C., Pigino, G., Yuan, M., Mori, H., & Yankner, B. A. (2002) · Neuron · doi:10.1016/s0896-6273(02)00604-9 · Cited by 387 · see citing works
β‐Site APP cleaving enzyme up‐regulation induced by 4‐hydroxynonenal is mediated by stress‐activated protein kinases pathways
Tamagno, E., Parola, M., Bardini, P., Piccini, A., Borghi, R., Guglielmotto, M., Santoro, G., Davit, A., Danni, O., Smith, M. A., et al. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02895.x · Cited by 324 · see citing works
Oxidative Stress in Alzheimer’s Disease: Why Did Antioxidant Therapy Fail?
Persson, T., Popescu, B. O., & Cedazo-Mı́nguez, Á. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/427318 · Cited by 317 · see citing works
Mitochondrial dysfunction, apoptotic cell death, and Alzheimer’s disease
Eckert, A., Keil, U., Marques, C. A., Bonert, A., Frey, C., Schüssel, K., & Müller, W. E. (2003) · Biochemical Pharmacology · doi:10.1016/s0006-2952(03)00534-3 · Cited by 309 · see citing works
Lactoferrin in a Context of Inflammation-Induced Pathology
Kruzel, M. L., Zimecki, M., & Actor, J. K. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01438 · Cited by 308 · see citing works
A Novel Function of Monomeric Amyloid β-Protein Serving as an Antioxidant Molecule against Metal-Induced Oxidative Damage
Zou, K., Gong, J.-S., Yanagisawa, K., & Michikawa, M. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-12-04833.2002 · Cited by 305 · see citing works
Aging and Alzheimer's disease: comparison and associations from molecular to system level
Xia, X., Jiang, Q., McDermott, J., & Han, J. J. (2018) · Aging Cell · doi:10.1111/acel.12802 · Cited by 301 · see citing works
Proteinopathy, oxidative stress and mitochondrial dysfunction: cross talk in Alzheimer's disease and Parkinson's disease
Ganguly, G., Chakrabarti, S., Chatterjee, U., & Saso, L. (2017) · Drug Design Development and Therapy · doi:10.2147/dddt.s130514 · Cited by 295 · see citing works
Alzheimer’s disease: pathological mechanisms and the beneficial role of melatonin
Rosales‐Corral, S., Acuña-Castroviejo, D., Coto‐Montes, A. M., Boga, J. A., Manchester, L. C., Fuentes‐Broto, L., Korkmaz, A., Ma, S., Tan, D. X., & Reiter, R. J. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00937.x · Cited by 293 · see citing works
Amyloid-β: a chameleon walking in two worlds: a review of the trophic and toxic properties of amyloid-β
Atwood, C., Obrenovich, M. E., Liu, T., Chan, H., Perry, G. L., Smith, M. A., & Martins, R. N. (2003) · Brain Research Reviews · doi:10.1016/s0165-0173(03)00174-7 · Cited by 292 · see citing works
Oxidative stress and β-amyloid protein in Alzheimer’s disease
Cai, Z., Zhao, B., & Ratka, A. (2011) · NeuroMolecular Medicine · doi:10.1007/s12017-011-8155-9 · Cited by 279 · see citing works
Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice
Li, F., Calingasan, N. Y., Yu, F., Mauck, W. M., Toidze, M., Almeida, C. G., Takahashi, R. H., Carlson, G. A., Beal, M. F., Lin, M. T. S., et al. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02455.x · Cited by 276 · see citing works
Hydrogen peroxide alters membrane and cytoskeleton properties and increases intercellular connections in astrocytes
Zhu, D., Tan, K. S., Zhang, X., Sun, A. Y., Sun, G. Y., & Lee, J. C.-M. (2005) · Journal of Cell Science · doi:10.1242/jcs.02507 · Cited by 264 · see citing works
Effects of Vitamin E on Lipid Peroxidation in Healthy Persons
Meagher, E. A. (2001) · JAMA · doi:10.1001/jama.285.9.1178 · Cited by 269 · see citing works
Protection against cognitive deficits and markers of neurodegeneration by long‐term oral administration of melatonin in a transgenic model of Alzheimer disease
Olcese, J., Cao, C., Mori, T., Mamcarz, M. B., Maxwell, A. K., Runfeldt, M. J., Wang, L., Zhang, C., Lin, X., Zhang, G., et al. (2009) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2009.00692.x · Cited by 260 · see citing works
Quercetin and rutin exhibit antiamyloidogenic and fibril-disaggregating effects in vitro and potent antioxidant activity in APPswe cells
Jiménez‐Aliaga, K., Bermejo‐Bescós, P., Benedı́, J., & Martín‐Aragón, S. (2011) · Life Sciences · doi:10.1016/j.lfs.2011.09.023 · Cited by 239 · see citing works
Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease
Mecocci, P. (2002) · Archives of Neurology · doi:10.1001/archneur.59.5.794 · Cited by 229 · see citing works
Neurotherapeutic applications of nanoparticles in Alzheimer’s disease
Sahni, J. K., Doggui, S., Ali, J., Baboota, S., Dao, L., & Ramassamy, C. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.11.033 · Cited by 219 · see citing works
Oxidative stress potentiates BACE1 gene expression and A? generation
Tong, Y., Zhou, W., Fung, V., Christensen, M. A., Qing, H., Sun, X., & Song, W. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-004-0255-3 · Cited by 219 · see citing works
Inflammatory mechanisms and oxidative stress as key factors responsible for progression of neurodegeneration: role of brain innate immune system
Leszek, J., E. Barreto, G., G|siorowski, K., Koutsouraki, E., Ávila-Rodrigues, M., & Aliev, G. (2016) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527315666160202125914 · Cited by 206 · see citing works
Cellular Proteostasis in Neurodegeneration
Kurtishi, A., Rosen, B., Patil, K. S., Alves, G. W., & Møller, S. G. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1334-z · Cited by 203 · see citing works
The role of mitochondrial dysfunction in age-related diseases
Lane, R. K., Hilsabeck, T., & Rea, S. L. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.021 · Cited by 205 · see citing works
Molecular Mechanisms and Genetics of Oxidative Stress in Alzheimer’s Disease
Cioffi, F., Adam, R. H. I., & Broersen, K. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190863 · Cited by 204 · see citing works
Oxidized cholesterol as the driving force behind the development of Alzheimer’s disease
Gamba, P., Testa, G., Gargiulo, S., Staurenghi, E., Poli, G., & Leonarduzzi, G. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00119 · Cited by 202 · see citing works
The α-ketoglutarate dehydrogenase complex in neurodegeneration
Gibson, G. E., Park, L. C. H., Sheu, K. R., Blass, J. P., & Calingasan, N. Y. (2000) · Neurochemistry International · doi:10.1016/s0197-0186(99)00114-x · Cited by 199 · see citing works
Antioxidant strategies for Alzheimer's disease
Grundman, M., & Delaney, P. (2002) · Proceedings of The Nutrition Society · doi:10.1079/pns2002146 · Cited by 193 · see citing works
A central role for dityrosine crosslinking of Amyloid-β in Alzheimer’s disease
Al‐Hilaly, Y. K., Williams, T. L., Stewart-Parker, M., Ford, L. K., Skaria, E., Cole, M., Bucher, W. G., Morris, K. L., Sada, A. A., Thorpe, J. R., et al. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-83 · Cited by 184 · see citing works
Iron: The Redox-active Center of Oxidative Stress in Alzheimer Disease
Castellani, R. J., Moreira, P. I., Liu, G., Dobson, J., Perry, G., Smith, M. A., & Zhu, X. (2007) · Neurochemical Research · doi:10.1007/s11064-007-9360-7 · Cited by 180 · see citing works
Combination Therapy in Alzheimer???s Disease: A Review of Current Evidence
Schmitt, B., Bernhardt, T., Moeller, H.-J., Heuser, I., & Fr??lich, L. (2004) · CNS Drugs · doi:10.2165/00023210-200418130-00001 · Cited by 182 · see citing works
The α-Ketoglutarate–Dehydrogenase Complex: A Mediator Between Mitochondria and Oxidative Stress in Neurodegeneration
Gibson, G. E., Blass, J. P., Beal, M. F., & Bunik, V. I. (2005) · Molecular Neurobiology · doi:10.1385/mn:31:1-3:043 · Cited by 178 · see citing works
Amyloid-β: an antioxidant that becomes a pro-oxidant and critically contributes to Alzheimer’s disease
Kontush, A. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00688-8 · Cited by 176 · see citing works
Luteinizing Hormone, a Reproductive Regulator That Modulates the Processing of Amyloid-β Precursor Protein and Amyloid-β Deposition
Bowen, R. L., Verdile, G., Liu, T., Parlow, A. F., Perry, G. L., Smith, M. A., Martins, R. N., & Atwood, C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311993200 · Cited by 174 · see citing works
Hydrogen Peroxide Promotes Aβ Production through JNK-dependent Activation of γ-Secretase
Shen, C., Chen, Y., Liu, H., Zhang, K., Zhang, T., Lin, A., & Jing, N. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800013200 · Cited by 168 · see citing works
JNK activation is associated with intracellular β-amyloid accumulation
Shoji, M., Iwakami, N., Takeuchi, S., Waragai, M., Suzuki, M., Kanazawa, I., Lippa, C. F., Ono, S., & Okazawa, H. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(00)00245-x · Cited by 166 · see citing works
AGEs/RAGE complex upregulates BACE1 via NF-κB pathway activation
Guglielmotto, M., Aragno, M., Tamagno, E., Vercellinatto, I., Visentin, S., Medana, C., Catalano, M. G., Smith, M. A., Perry, G. L., Danni, O., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.05.026 · Cited by 162 · see citing works
Coenzyme Q10 Decreases Amyloid Pathology and Improves Behavior in a Transgenic Mouse Model of Alzheimer's Disease
Dumont, M., Kipiani, K., Yu, F., Wille, E. J., Katz, M., Calingasan, N. Y., Gouras, G. K., Lin, M. T. S., & Beal, M. F. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110209 · Cited by 161 · see citing works
Oxidative Stress and Transcriptional Regulation in Alzheimer Disease
Shi, Q., & Gibson, G. E. (2007) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31815721c3 · Cited by 156 · see citing works
BACE1 Suppression by RNA Interference in Primary Cortical Neurons
Kao, S.-C., Krichevsky, A. M., Kosik, K. S., & Tsai, L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309219200 · Cited by 152 · see citing works
Oxidative Imbalance in Alzheimer's Disease
Zhu, X., Lee, H., Casadesús, G., Ávila, J., Drew, K. L., Perry, G. L., & Smith, M. A. (2005) · Molecular Neurobiology · doi:10.1385/mn:31:1-3:205 · Cited by 146 · see citing works
Oxidative stress: A bridge between Down's syndrome and Alzheimer's disease
Zana, M., Janka, Z., & Kalman, J. L. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.03.008 · Cited by 137 · see citing works
Oxidative stress mediates the pathogenic effect of different Alzheimer’s disease risk factors
Guglielmotto, M. (2010) · Frontiers in Aging Neuroscience · doi:10.3389/neuro.24.003.2010 · Cited by 133 · see citing works
Vitamin E reduces amyloidosis and improves cognitive function in Tg2576 mice following repetitive concussive brain injury
Conte, V., Uryu, K., Fujimoto, S., Yao, Y., Rokach, J., Longhi, L., Trojanowski, J. Q., Lee, V. M., McIntosh, T. K., & Praticò, D. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02560.x · Cited by 164 · see citing works
Pathophysiology of Alzheimer's Disease
Imbimbo, B. P., Lombard, J., & Pomara, N. (2005) · Neuroimaging Clinics of North America · doi:10.1016/j.nic.2005.09.009 · Cited by 133 · see citing works
Neuronal death in Alzheimer’s disease and therapeutic opportunities
Donev, R., Kolev, M. V., Millet, B., & Thome, J. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00889.x · Cited by 124 · see citing works
Oxidative stress induces DNA demethylation and histone acetylation in SH-SY5Y cells: potential epigenetic mechanisms in gene transcription in Aβ production
Gu, X., Sun, J., Li, S., Wu, X., & Li, L. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.10.013 · Cited by 127 · see citing works
Deficiency of TYROBP, an adapter protein for TREM2 and CR3 receptors, is neuroprotective in a mouse model of early Alzheimer’s pathology
Haure-Mirande, J.-V., Audrain, M., Fanutza, T., Kim, S. H., Klein, W. L., Glabe, C., Readhead, B., Dudley, J. T., Blitzer, R. D., Wang, M., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1737-3 · Cited by 127 · see citing works
The α‐Ketoglutarate Dehydrogenase Complex
Sheu, K. R., & Blass, J. P. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07818.x · Cited by 125 · see citing works
New Insights into the Role of Mitochondrial Dynamics and Autophagy during Oxidative Stress and Aging in the Heart
Ikeda, Y., Sciarretta, S., Nagarajan, N., Rubattu, S., Volpe, M., Frati, G., & Sadoshima, J. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/210934 · Cited by 124 · see citing works
Telomere Shortening and Alzheimer’s Disease
Cai, Z., Yan, L., & Ratka, A. (2012) · NeuroMolecular Medicine · doi:10.1007/s12017-012-8207-9 · Cited by 120 · see citing works
The mitochondria-targeted antioxidant MitoQ inhibits memory loss, neuropathology, and extends lifespan in aged 3xTg-AD mice
Young, M. L., & Franklin, J. L. (2019) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2019.103409 · Cited by 120 · see citing works
Lipid peroxidation up‐regulates BACE1 expression in vivo : a possible early event of amyloidogenesis in Alzheimer’s disease
Chen, L., Na, R., Gu, M., Richardson, A. G., & Ran, Q. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05603.x · Cited by 119 · see citing works
Milk-derived proteins and peptides of potential therapeutic and nutritive value.
Zimecki, M., & Kruzel, M. L. (2007) · PubMed · Cited by 117 · see citing works
Amyloid β−Cu2+Complexes in both Monomeric and Fibrillar Forms Do Not Generate H2O2Catalytically but Quench Hydroxyl Radicals
Nadal, R. C., Rigby, S. E. J., & Viles, J. H. (2008) · Biochemistry · doi:10.1021/bi8011093 · Cited by 118 · see citing works
Amyloid-β Induces Smac Release via AP-1/Bim Activation in Cerebral Endothelial Cells
Yin, K., Lee, J., Chen, S., Xu, J., & Hsu, C. Y. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-22-09764.2002 · Cited by 117 · see citing works
Amyloid-β Production: Major Link Between Oxidative Stress and BACE1
Tamagno, E., Guglielmotto, M., Monteleone, D., & Tabaton, M. (2011) · Neurotoxicity Research · doi:10.1007/s12640-011-9283-6 · Cited by 115 · see citing works
Coenzyme Q10 Attenuates β-Amyloid Pathology in the Aged Transgenic Mice with Alzheimer Presenilin 1 Mutation
Yang, X., Yang, Y., Li, G., Wang, J., & Yang, E. S. (2008) · Journal of Molecular Neuroscience · doi:10.1007/s12031-007-9033-7 · Cited by 111 · see citing works
Nutraceutical and Health-Promoting Potential of Lactoferrin, an Iron-Binding Protein in Human and Animal: Current Knowledge
Ashraf, M. F., Zubair, D., Bashir, M. N., Alagawany, M. M., Ahmed, S., Shah, Q. A., Buzdar, J. A., & Arain, M. A. (2023) · Biological Trace Element Research · doi:10.1007/s12011-023-03658-4 · Cited by 111 · see citing works
Membrane-mediated Amyloidogenesis and the Promotion of Oxidative Lipid Damage by Amyloid β Proteins
Murray, I. V. J., Liu, L., Komatsu, H., Uryu, K., Xiao, G., Lawson, J. A., & Axelsen, P. H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608589200 · Cited by 106 · see citing works
Supplemental Use of Antioxidant Vitamins and Subsequent Risk of Cognitive Decline and Dementia
Maxwell, C. J., Hicks, M. S., Hogan, D. B., Basran, J., & Ebly, E. M. (2005) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000085074 · Cited by 105 · see citing works
Inflammation, genes and zinc in Alzheimer's disease
Vasto, S., Candore, G., Listı̀, F., Balistreri, C. R., Colonna‐Romano, G., Malavolta, M., Lio, D., Nuzzo, D., Mocchegiani, E., Bona, D. D., et al. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.12.001 · Cited by 104 · see citing works
Stabilization of transcription factor Nrf2 by tBHQ prevents oxidative stress-induced amyloid β formation in NT2N neurons
Eftekharzadeh, B., Maghsoudi, N., & Khodagholi, F. (2009) · Biochimie · doi:10.1016/j.biochi.2009.12.001 · Cited by 102 · see citing works
RETRACTED ARTICLE: Chitosan prevents oxidative stress-induced amyloid β formation and cytotoxicity in NT2 neurons: involvement of transcription factors Nrf2 and NF-κB
Khodagholi, F., Eftekharzadeh, B., Maghsoudi, N., & Rezaei, P. F. (2009) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-009-0284-1 · Cited by 102 · see citing works
Retracted
Oxidative stress underlying axonal degeneration in adrenoleukodystrophy: A paradigm for multifactorial neurodegenerative diseases?
Galea, E., Launay, N., Portero-Otin, M., Ruiz, M., Pamplona, R., Aubourg, P., Ferrer, I., & Pujol, A. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.02.005 · Cited by 108 · see citing works
Oxidative Stress and Aging as Risk Factors for Alzheimer’s Disease and Parkinson’s Disease: The Role of the Antioxidant Melatonin
Tchekalarova, J. D., & Tzoneva, R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24033022 · Cited by 100 · see citing works
Autophagy, Cellular Aging and Age-related Human Diseases
Cheon, S. Y., Kim, H. J., Rubinsztein, D. C., & Lee, J. E. (2019) · Experimental Neurobiology · doi:10.5607/en.2019.28.6.643 · Cited by 92 · see citing works
Palmitic acid-treated astrocytes induce BACE1 upregulation and accumulation of C-terminal fragment of APP in primary cortical neurons
Patil, S. P., Sheng, L., Masserang, A., & Chan, C. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.07.015 · Cited by 93 · see citing works
New Insights in Amyloid Beta Interactions with Human Telomerase
Wang, J., Zhao, C., Zhao, A., Li, M., Ren, J., & Qu, X. (2015) · Journal of the American Chemical Society · doi:10.1021/ja511030s · Cited by 90 · see citing works
Alginate protects NT2 neurons against H2O2-induced neurotoxicity
Eftekharzadeh, B., Khodagholi, F., Abdi, A., & Maghsoudi, N. (2009) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2009.10.040 · Cited by 89 · see citing works
The role of glycogen synthase kinase 3 in the early stages of Alzheimers’ disease
Hernández, F., & Ávila, J. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.10.026 · Cited by 86 · see citing works
Repeated Sauna Therapy Reduces Urinary 8-Epi-Prostaglandin F2.ALPHA.
Masuda, A., Miyata, M., Kihara, T., Minagoe, S., & Tei, C. (2004) · Japanese Heart Journal · doi:10.1536/jhj.45.297 · Cited by 86 · see citing works
Cathepsin D–Bax death pathway in oxidative stressed neuroblastoma cells
Castino, R., Bellio, N., Nicotra, G., Follo, C., Trincheri, N. F., & Isidoro, C. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.12.030 · Cited by 86 · see citing works
P2Y2 Nucleotide Receptor-Mediated Responses in Brain Cells
Peterson, T. S., Camden, J. M., Wang, Y., Seye, C. I., Wood, W. G., Sun, G. Y., Erb, L., Petris, M. J., & Weisman, G. A. (2010) · Molecular Neurobiology · doi:10.1007/s12035-010-8115-7 · Cited by 84 · see citing works
β-amyloid 42 accumulation in the lumbar spinal cord motor neurons of amyotrophic lateral sclerosis patients
Calingasan, N. Y., Chen, J., Kiaei, M., & Beal, M. F. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.01.012 · Cited by 81 · see citing works
A combination of an iron chelator with an antioxidant effectively diminishes the dendritic loss, tau-hyperphosphorylation, amyloids-β accumulation and brain mitochondrial dynamic disruption in rats with chronic iron-overload
Sripetchwandee, J., Wongjaikam, S., Krintratun, W., Chattipakorn, N., & Chattipakorn, S. C. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.07.003 · Cited by 82 · see citing works
Thiamine deficiency increases β-secretase activity and accumulation of β-amyloid peptides
Zhang, Q., Yang, G., Li, W., Fan, Z., Sun, A., Luo, J., & Ke, Z. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.01.005 · Cited by 82 · see citing works
The increased activity of BACE1 correlates with oxidative stress in Alzheimer's disease
Borghi, R., Patriarca, S., Traverso, N., Piccini, A., Storace, D., Garuti, A., Cirmena, G., Odetti, P. R., & Tabaton, M. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.05.004 · Cited by 82 · see citing works
Aluminum‐induced pro‐oxidant effects in rats: protective role of exogenous melatonin
Esparza, J. L., Gómez, M., Romeu, M., Mulero, M., Sánchez, D. J., Mallol, J., & Domingo, J. L. (2003) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2003.00048.x · Cited by 82 · see citing works
Epicatechin and Catechin in Cocoa Inhibit Amyloid β Protein Induced Apoptosis
Heo, H. J., & Lee, C. Y. (2005) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf048989m · Cited by 82 · see citing works
Oxidative Stress and Hypoxia Contribute to Alzheimer's Disease Pathogenesis: Two Sides of the Same Coin
Guglielmotto, M., Tamagno, E., & Danni, O. (2009) · The Scientific World JOURNAL · doi:10.1100/tsw.2009.93 · Cited by 81 · see citing works
The role of iron as a mediator of oxidative stress in Alzheimer disease
Castellani, R. J., Moreira, P. I., Perry, G. L., & Zhu, X. (2012) · BioFactors · doi:10.1002/biof.1010 · Cited by 82 · see citing works
The state versus amyloid-β: the trial of the most wanted criminal in Alzheimer disease
Rottkamp, C. A., Atwood, C., Joseph, J. A., Nunomura, A., Perry, G. L., & Smith, M. A. (2002) · Peptides · doi:10.1016/s0196-9781(02)00069-4 · Cited by 80 · see citing works
Intraneuronal amyloid β accumulation and oxidative damage to nucleic acids in Alzheimer disease
Nunomura, A., Tamaoki, T., Tanaka, K., Motohashi, N., Nakamura, M., Hayashi, T., Yamaguchi, H., Shimohama, S., Lee, H., Zhu, X., et al. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.12.012 · Cited by 80 · see citing works
Comparative study of the effects of phosphatidylcholine rich in DHA and EPA on Alzheimer's disease and the possible mechanisms in CHO-APP/PS1 cells and SAMP8 mice
Che, H., Zhou, M., Zhang, T., Zhang, L., Ding, L., Yanagita, T., Xu, J., Xue, C., & Wang, Y. (2017) · Food & Function · doi:10.1039/c7fo01342f · Cited by 79 · see citing works
Anti-amnesic effect of pseudoginsenoside-F11 in two mouse models of Alzheimer's disease
Wang, C., Liu, M.-Y., Wang, F., Wei, M., Wang, S., Wu, C., & Yang, J. (2013) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2013.03.010 · Cited by 79 · see citing works

Oxidative Stress Induces Intralysosomal Accumulation of Alzheimer Amyloid β‐Protein in Cultured Neuroblastoma Cells
Zheng, L. P., Roberg, K. B., Jerhammar, F., Marcusson, J. O., & Terman, A. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1354.032 · Cited by 35 · see citing works
P3–361: Intralysosomal localization of APP and ΑΒ in cultured cells exposed to oxidative stress
Zheng, L. P., Paulsson, Y., Jonasson, M., Marcusson, J. O., & Terman, A. (2006) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2006.05.1631
Oxidative stress increases levels of endogenous amyloid‐β peptides secreted from primary chick brain neurons
Goldsbury, C. S., Whiteman, I. T., Jeong, E. V., & Lim, Y. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2008.00423.x · Cited by 43 · see citing works
Autophagy of amyloid beta-protein in differentiated neuroblastoma cells exposed to oxidative stress
Zheng, L. P., Roberg, K. B., Jerhammar, F., Marcusson, J. O., & Terman, A. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.10.035 · Cited by 49 · see citing works
Overexpression of amyloid precursor protein induces susceptibility to oxidative stress in human neuroblastoma SH-SY5Y cells
Matsumoto, K., Akao, Y., Yi, H. L., Shamoto‐Nagai, M., Maruyama, W., & Naoi, M. (2005) · Journal of Neural Transmission · doi:10.1007/s00702-005-0318-0 · Cited by 33 · see citing works

Authors: Misonou, H., Morishima-Kawashima, M., & Ihara, Y.
Affiliations: Japan Science and Technology Agency (JP)
Department of Neuropathology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, and Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Kawaguchi, Saitama 332-0012, Japan
Corresponding author: Ihara, Yasuo
ORCID: Misonou, Hiroaki
Ihara, Yasuo
Venue: Biochemistry
Publisher: American Chemical Society (ACS)
Published: 2000-05-19
Volume: 39
Issue: 23
Pages: 6951-6959
ISSN: 0006-2960 (ISSN-L)
1520-4995
DOI: 10.1021/bi000169p
OpenAlex: W2048360633
Cited by: 304
References: 19
Citations by year: 2026: 4 · 2025: 3 · 2024: 11 · 2023: 12 · 2022: 6 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 19 · 2017: 14 · 2016: 12 · 2015: 10 · 2014: 13 · 2013: 8 · 2012: 15
FWCI: 6.80
Type: journal article
Language: en
Open access: closed
Locations: Biochemistry (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: oxidative stress, amyloid-beta, Alzheimer's disease, hydrogen peroxide, amyloid precursor protein, APP cleavage, amyloidogenic pathway, intracellular accumulation, SH-SY5Y cells, protein half-life, amyloid plaques
MeSH terms: Alzheimer Disease, Animals, Antioxidants, Cell Survival, Chromans, Dimethyl Sulfoxide, Cricetinae, Humans, Hydrogen Peroxide, Neuroblastoma, Peptide Fragments, Phosphatidylserines, RNA, Messenger, Tetrazolium Salts, Thiazoles, Transfection, Tumor Cells, Cultured, Amyloid beta-Peptides, CHO Cells, Amyloid beta-Protein Precursor, Apoptosis, Oxidative Stress

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

Oxidative Stress Induces Intracellular Accumulation of Amyloid β-Protein (Aβ) in Human Neuroblastoma Cells

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks