Rapid cell death is preceded by amyloid plaque-mediated oxidative stress
Open accessAbstract
Neuronal loss is the ultimate outcome in a variety of neurodegenerative diseases and central nerve system disorders. Understanding the sequelae of events that leads to cell death would provide insight into neuroprotective approaches. We imaged neurons in the living brain of a mouse model of Alzheimer's disease that overexpresses mutant human amyloid precursor protein and presenilin 1 and followed the death of individual neurons in real time. This mouse model exhibited limited neurodegeneration and atrophy, but we were able to identify a small fraction of vulnerable cells that would not have been detectable by using standard approaches. By exploiting a genetically encoded reporter of oxidative stress, we identified susceptible neurons by their increased redox potential. The oxidative stress was most dramatic in neurites near plaques, propagated to cell bodies, and preceded activation of caspases that led to cell death within 24 h. Thus, local oxidative stress surrounding plaques contributes to long-range toxicity and selective neuronal death in Alzheimer's disease.
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Local oxidative stress surrounding plaques has been proposed as a potential mechanism contributing to selective neuronal death.
“and local oxidative stress surrounding plaques has been proposed as a potential mechanism contributing to selective neuronal death [37].”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [37]
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Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455 · see citing works
Oxidative stress and neurodegeneration: where are we now?
Halliwell, B. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03907.x · Cited by 2,614 · see citing works
Oxidative stress hypothesis in Alzheimer’s disease
Markesbery, W. R. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00629-6 · Cited by 2,383 · see citing works
Bard, F., Cannon, C., Barbour, R., Burke, R.-L., Games, D., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., et al. (2000) · Nature Medicine · doi:10.1038/78682 · Cited by 2,012 · see citing works
Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease.
Smith, C. D., Carney, J. M., Starke-Reed, P. E., Oliver, C. N., Stadtman, E. R., Floyd, R. A., & Markesbery, W. R. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.23.10540 · Cited by 1,296 · see citing works
Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease
Mecocci, P., MacGarvey, U., & Beal, M. F. (1994) · Annals of Neurology · doi:10.1002/ana.410360510 · Cited by 1,037 · see citing works
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
Borchelt, D. R., Ratovitski, T., van Lare, J., Lee, M. K., Gonzales, V., Jenkins, N. A., Copeland, N. G., Price, D. L., & Sisodia, S. S. (1997) · Neuron · doi:10.1016/s0896-6273(00)80974-5 · Cited by 1,023 · see citing works
Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer’s disease
Meyer-Luehmann, M., Spires-Jones, T. L., Prada, C., Garcia-Alloza, M., de Calignon, A., Rozkalne, A., Koenigsknecht-Talboo, J., Holtzman, D. M., Bacskai, B. J., & Hyman, B. T. (2008) · Nature · doi:10.1038/nature06616 · Cited by 987 · see citing works
Self-citationKoffie, R. M., Meyer-Luehmann, M., Hashimoto, T., Adams, K. W., Mielke, M. L., Garcia-Alloza, M., Micheva, K. D., Smith, S. J., Kim, M. L., Lee, V. M., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811698106 · Cited by 850 · see citing works
Praticò, D., Uryu, K., Leight, S., Trojanoswki, J. Q., & Lee, V. M.-Y. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-12-04183.2001 · Cited by 777 · see citing works
Imaging Dynamic Redox Changes in Mammalian Cells with Green Fluorescent Protein Indicators
Dooley, C. T., Dore, T. M., Hanson, G. T., Jackson, W. C., Remington, S. J., & Tsien, R. Y. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312847200 · Cited by 776 · see citing works
Lovell, M. A., Ehmann, W. D., Butler, S. M., & Markesbery, W. R. (1995) · Neurology · doi:10.1212/wnl.45.8.1594 · Cited by 644 · see citing works
Kuchibhotla, K. V., Goldman, S. T., Lattarulo, C. R., Wu, H.-Y., Hyman, B. T., & Bacskai, B. J. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.008 · Cited by 614 · see citing works
Oxidative stress hypothesis in Alzheimer’s disease: a reappraisal
Praticò, D. (2008) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2008.09.001 · Cited by 606 · see citing works
Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches
Tsai, J., Grutzendler, J., Duff, K., & Gan, W.-B. (2004) · Nature Neuroscience · doi:10.1038/nn1335 · Cited by 561 · see citing works
Spires, T. L., Meyer-Luehmann, M., Stern, E. A., McLean, P. J., Skoch, J., Nguyen, P. T., Bacskai, B. J., & Hyman, B. T. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1879-05.2005 · Cited by 550 · cited 5× · see citing works
“Flanked by the ITRs, the expression cassette included the following components: (i) a 1.7-kb sequence containing hybrid cytomegalovirus immediateearly enhancer/chicken β-actin promoter/exon1/intron; (ii) roGFP1; and (iii) WPRE.”
BackgroundMethodInfluentialCaspase activation precedes and leads to tangles
de Calignon, A., Fox, L. M., Pitstick, R., Carlson, G. A., Bacskai, B. J., Spires-Jones, T. L., & Hyman, B. T. (2010) · Nature · doi:10.1038/nature08890 · Cited by 517 · see citing works
Self-citationIncreased peroxidation and reduced antioxidant enzyme activity in Alzheimer's disease
Marcus, D. L., Thomas, C., Rodriguez, C., Simberkoff, K., Tsai, J. S., Strafaci, J. A., & Freedman, M. L. (1998) · Experimental Neurology · doi:10.1006/exnr.1997.6750 · Cited by 513 · see citing works
Autopsy Samples of Alzheimer's Cortex Show Increased Peroxidation In Vitro
Subbarao, K. V., Richardson, J. S., & Ang, L. C. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb08858.x · Cited by 463 · see citing works
Pratico, D., Lee, V. M.-Y., Trojanowski, J. Q., Rokach, J., & Fitzgerald, G. A. (1998) · The FASEB Journal · doi:10.1096/fasebj.12.15.1777 · Cited by 405 · see citing works
Butterfield, D. A., Poon, H. F., St. Clair, D., Keller, J. N., Pierce, W. M., Klein, J. B., & Markesbery, W. R. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.11.002 · Cited by 377 · see citing works
Harris‐White, M. E., Hensley, K., Butterfield, D. A., Leedle, R. A., & Carney, J. M. (1995) · Experimental Neurology · doi:10.1016/0014-4886(95)90041-1 · Cited by 331 · see citing works
Non-Fc-Mediated Mechanisms Are Involved in Clearance of Amyloid-β<i>In Vivo</i>by Immunotherapy
Bacskai, B. J., Kajdasz, S. T., McLellan, M. E., Games, D., Seubert, P., Schenk, D., & Hyman, B. T. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-18-07873.2002 · Cited by 323 · see citing works
Blanchard, V., Moussaoui, S., Czech, C., Touchet, N., Bonici, B., Planche, M., Canton, T., Jedidi, I., Gohin, M., Wirths, O., et al. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00252-8 · Cited by 283 · see citing works
Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment
Wang, J., Markesbery, W. R., & Lovell, M. A. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03615.x · Cited by 260 · see citing works
McLellan, M. E., Kajdasz, S. T., Hyman, B. T., & Bacskai, B. J. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-06-02212.2003 · Cited by 174 · see citing works
Re‐engineering redox‐sensitive green fluorescent protein for improved response rate
Cannon, M. B., & Remington, S. J. (2005) · Protein Science · doi:10.1110/ps.051734306 · Cited by 91 · see citing works
Cannon, M. B., & Remington, S. J. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-129-1_4 · Cited by 60 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [30]Spires TL, et al. Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy. J Neurosci. 2005;25(31):7278–7287. doi: 10.1523/JNEUROSCI.1879-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
Cited by
Sorted by citations
Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease
Wang, X., Wang, W., Li, L., Perry, G., Lee, H.-G., & Zhu, X. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.10.015 · Cited by 1,357 · see citing works
Grubman, A., Chew, G., Ouyang, J. F., Sun, G., Choo, X. Y., McLean, C., Simmons, R. K., Buckberry, S., Vargas-Landin, D. B., Poppe, D., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0539-4 · Cited by 956 · see citing works
Glial Lipid Droplets and ROS Induced by Mitochondrial Defects Promote Neurodegeneration
Liu, L., Zhang, K., Sandoval, H., Yamamoto, S., Jaiswal, M., Sanz, E., Li, Z., Hui, J., Graham, B. H., Quintana, A., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.019 · Cited by 876 · see citing works
Understanding mechanisms of antioxidant action in health and disease
Halliwell, B. B. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00645-4 · Cited by 674 · see citing works
Jiang, T., Sun, Q., & Chen, S. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.07.005 · Cited by 594 · see citing works
Calvo-Rodríguez, M., Hou, S. S., Snyder, A. C., Kharitonova, E. K., Russ, A., Das, S., Fan, Z., Muzikansky, A., Garcı́a-Alloza, M., Serrano‐Pozo, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16074-2 · Cited by 432 · see citing works
Lactate and pyruvate promote oxidative stress resistance through hormetic ROS signaling
Tauffenberger, A., Fiumelli, H., Almustafa, S., & Magistretti, P. J. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1877-6 · Cited by 345 · see citing works
Sadleir, K. R., Kandalepas, P. C., Buggia-Prévot, V., Nicholson, D. A., Thinakaran, G., & Vassar, R. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1558-9 · Cited by 294 · see citing works
Dissecting Redox Biology Using Fluorescent Protein Sensors
Schwarzländer, M., Dick, T. P., Meyer, A. J., & Morgan, B. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6266 · Cited by 298 · see citing works
Mitochondria and Calcium in Alzheimer’s Disease: From Cell Signaling to Neuronal Cell Death
Calvo-Rodriguez, M., & Bacskai, B. J. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2020.10.004 · Cited by 254 · see citing works
Role of Copper in the Onset of Alzheimer’s Disease Compared to Other Metals
Bagheri, S., Squitti, R., Haertlé, T., Siotto, M., & Saboury, A. A. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00446 · Cited by 231 · see citing works
The role of different SIRT1-mediated signaling pathways in toxic injury
Ren, Z., He, H., Zuo, Z., Xu, Z., Wei, Z., & Deng, J. (2019) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-019-0158-9 · Cited by 192 · see citing works
Mitochondrial alterations near amyloid plaques in an Alzheimer’s disease mouse model
Xie, H., Guan, J., Borrelli, L. A., Xu, J., Serrano-Pozo, A., & Bacskai, B. J. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1836-13.2013 · Cited by 185 · see citing works
“roGFP was introduced into the construct pAAV-CBA-roGFP1-WPRE and the ratio of the emission fluorescence excited at 800 and 900 nm was used as an index of the redox status of roGFP (Xie et al., 2013).”
BackgroundMethodInfluentialBuccellato, F. R., D’Anca, M., Fenoglio, C., Scarpini, E., & Galimberti, D. (2021) · Antioxidants · doi:10.3390/antiox10091353 · Cited by 179 · see citing works
Antioxidant gene therapy against neuronal cell death
Navarro-Yepes, J., Zavala-Flores, L. M., Anandhan, A., Wang, F., Skotak, M., Chandra, N., Li, M., Pappa, A., Martínez‐Fong, D., Razo, L. M. D., et al. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.12.007 · Cited by 177 · see citing works
Lü, Y., Guo, Z., Zhang, Y., Li, C., Zhang, Y., Guo, Q., Chen, Q., Chen, X., He, X., Liu, L., et al. (2018) · Advanced Science · doi:10.1002/advs.201801586 · Cited by 162 · see citing works
Oxidative stress and lipid peroxidation are upstream of amyloid pathology
Arimon, M., Takeda, S., Post, K. E., Svirsky, S. E., Hyman, B. T., & Berezovska, O. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.06.013 · Cited by 155 · see citing works
Ullah, R., Khan, M., Shah, S. A., Saeed, K. M., & Kim, M. O. (2019) · Nutrients · doi:10.3390/nu11061195 · Cited by 154 · see citing works
Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches
Ijaz, H. W., Wang, W., & Lang, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207660 · Cited by 146 · see citing works
Konno, T., Melo, E. P., Chambers, J. E., & Avezov, E. (2021) · Cells · doi:10.3390/cells10020233 · Cited by 140 · see citing works
Mitochondrial Dysfunction in Alzheimer’s Disease: A Biomarker of the Future?
Bell, S., Barnes, K., Marco, M. D., Shaw, P. J., Ferraiuolo, L., Blackburn, D. J., Venneri, A., & Mortiboys, H. (2021) · Biomedicines · doi:10.3390/biomedicines9010063 · Cited by 136 · see citing works
Liu, P., Zhang, T., Chen, Q., Li, C., Chu, Y., Guo, Q., Zhang, Y., Zhou, W., Chen, H., Zhou, Z., et al. (2021) · Advanced Materials · doi:10.1002/adma.202100746 · Cited by 137 · see citing works
Yang, J., Zhang, X., Yuan, P., Yang, J., Xu, Y., Grutzendler, J., Shao, Y., Moore, A. V., & Ran, C. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1706248114 · Cited by 133 · see citing works
Villavicencio-Tejo, F., & Quintanilla, R. A. (2021) · Antioxidants · doi:10.3390/antiox10071069 · Cited by 135 · see citing works
Zhang, J., Cao, Q., Li, S., Lu, X., Zhao, Y., Guan, J., Chen, J., Wu, Q., & Chen, G. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.06.043 · Cited by 130 · see citing works
Astroglial connexin43 contributes to neuronal suffering in a mouse model of Alzheimer’s disease
Yi, C., Mei, X., Ezan, P., Mato, S., Matias, I., Giaume, C., & Koulakoff, A. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.63 · Cited by 127 · see citing works
Rahman, S. O., Panda, B. P., Parvez, S., Kaundal, M., Hussain, S., Akhtar, M., & Najmi, A. K. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.11.043 · Cited by 129 · see citing works
Benseny‐Cases, N., Klementieva, O. L., Cotte, M., Ferrer, I., & Cladera, J. (2014) · Analytical Chemistry · doi:10.1021/ac502667b · Cited by 121 · see citing works
Zhang, J., Shi, R., Li, H., Xiang, Y., Xiao, L., Hu, M., Ma, F., Ma, C. W., & Huang, Z. (2016) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2016.09.031 · Cited by 110 · see citing works
Molecular crosstalk between cancer and neurodegenerative diseases
Seo, J., & Park, M. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03428-3 · Cited by 106 · see citing works
Yi, C., Ezan, P., Fernández, P., Schmitt, J., Sáez, J. C., Giaume, C., & Koulakoff, A. (2017) · Glia · doi:10.1002/glia.23182 · Cited by 104 · see citing works
The Ubiquitin-Proteasome System and Molecular Chaperone Deregulation in Alzheimer’s Disease
Sulistio, Y. A., & Heese, K. (2015) · Molecular Neurobiology · doi:10.1007/s12035-014-9063-4 · Cited by 93 · see citing works
Park, J., Choi, H., Min, J., Kim, B., Lee, S., Yun, J. W., Choi, M., Chang, K., & Lee, D. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.12984 · Cited by 93 · see citing works
Calvo-Rodríguez, M., Kharitonova, E. K., Snyder, A. C., Hou, S. S., Sanchez-Mico, M. V., Das, S., Fan, Z., Shirani, H., Nilsson, K. P. R., Serrano‐Pozo, A., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00702-2 · Cited by 97 · see citing works
Karvandi, M. S., Hesari, F. S., Aref, A. R., & Mahdavi, M. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1105247 · Cited by 94 · see citing works
Kapila, A. K., Watts, H. R., Wang, T., & Ma, D. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132258 · Cited by 86 · see citing works
Kim, B., Park, J., Chang, K., & Lee, D. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.11.015 · Cited by 84 · see citing works
Prasad, K. N. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.01.002 · Cited by 82 · see citing works
Sancataldo, G., Vetri, V., Foderà, V., Cara, G. D., Militello, V., & Leone, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0084552 · Cited by 79 · see citing works
Xie, H. B., Liu, Y., Zhu, Y., Ding, X., Yang, Y., & Guan, J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1316808111 · Cited by 78 · see citing works
Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models
Wirths, O., & Zampar, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218144 · Cited by 75 · see citing works
“Nonetheless, thioflavin S-positive fibrillary Aβ deposits contribute to focal neuronal toxicity, at least in their immediate environment, as shown in both AD cases and AD transgenic mice [36] and local oxidative stress surrounding plaques has been proposed as a potential mechanism contributing to selective neuronal de…”
BackgroundThe Bewildering Effect of AMPK Activators in Alzheimer’s Disease: Review of the Current Evidence
Assefa, B. T., Tafere, G. G., Wondafrash, D. Z., & Gidey, M. T. (2020) · BioMed Research International · doi:10.1155/2020/9895121 · Cited by 75 · see citing works
van Creveld, S. G., Rosenwasser, S., Schatz, D., Koren, I., & Vardi, A. (2014) · The ISME Journal · doi:10.1038/ismej.2014.136 · Cited by 75 · see citing works
eEF2K inhibition blocks Aβ42 neurotoxicity by promoting an NRF2 antioxidant response
Jan, A., Jansonius, B., Delaidelli, A., Somasekharan, S. P., Bhanshali, F., Vandal, M., Negri, G. L., Moerman, D. G., Mackenzie, I. R., Calon, F., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1634-1 · Cited by 73 · see citing works
Röhr, D., Boon, B. D. C., Schuler, M., Kremer, K., Hoozemans, J. J. M., Bouwman, F. H., El-Mashtoly, S. F., Nabers, A., Großerueschkamp, F., Rozemuller, A. J. M., et al. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01091-5 · Cited by 77 · see citing works
New tools for redox biology: From imaging to manipulation
Bilan, D. S., & Belousov, V. V. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.004 · Cited by 69 · see citing works
Dietary natural products as epigenetic modifiers in aging-associated inflammation and disease
Evans, L. W., Stratton, M. S., & Ferguson, B. S. (2020) · Natural Product Reports · doi:10.1039/c9np00057g · Cited by 70 · see citing works
Moulin, M., & Ferreiro, A. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.08.003 · Cited by 65 · see citing works
Hypometabolism, Alzheimer’s Disease, and Possible Therapeutic Targets: An Overview
Raut, S., Bhalerao, A., Powers, M., Gonzalez, M., Mancuso, S., & Cucullo, L. (2023) · Cells · doi:10.3390/cells12162019 · Cited by 65 · see citing works
In Vivo Imaging with Genetically Encoded Redox Biosensors
Kostyuk, A. I., Panova, A. S., Kokova, A. D., Kotova, D. A., Maltsev, D. I., Podgorny, O. V., Belousov, V. V., & Bilan, D. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218164 · Cited by 63 · see citing works
Apelin/APJ system: A novel promising target for neurodegenerative diseases
Luo, H., Han, L., & Xu, J. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.29001 · Cited by 61 · see citing works
A Versatile, Portable Intravital Microscopy Platform for Studying Beta-cell Biology In Vivo
Reissaus, C. A., Piñeros, A. R., Twigg, A. N., Orr, K. S., Conteh, A. M., Irizarry, M. M. M., Kamocka, M. M., Day, R. N., Tersey, S. A., Mirmira, R. G., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-44777-0 · Cited by 52 · see citing works
Bi, R., Zhang, W., Zhang, D., Xu, M., Fan, Y., Hu, Q.-X., Jiang, H., Tan, L., Li, T., Fang, Y., et al. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0144-3 · Cited by 53 · see citing works
Activators of Nrf2 to Counteract Neurodegenerative Diseases
Amoroso, R., Maccallini, C., & Bellezza, I. (2023) · Antioxidants · doi:10.3390/antiox12030778 · Cited by 49 · see citing works
CART treatment improves memory and synaptic structure in APP/PS1 mice
Jin, J., Liou, A. K. F., Shi, Y., Yin, K., Chen, L., Li, L., Zhu, X., Qian, L., Yang, R., Chen, J., et al. (2015) · Scientific Reports · doi:10.1038/srep10224 · Cited by 48 · see citing works
Curcumin Scaffold as a Multifunctional Tool for Alzheimer’s Disease Research
Yang, H., Zeng, F., Luo, Y., Zheng, C., Ran, C., & Yang, J. (2022) · Molecules · doi:10.3390/molecules27123879 · Cited by 49 · see citing works
In Vivo Imaging of Microglia With Multiphoton Microscopy
Hierro‐Bujalance, C., Bacskai, B. J., & Garcı́a-Alloza, M. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00218 · Cited by 49 · see citing works
Pulse Pressure: An Emerging Therapeutic Target for Dementia
Levin, R., Carnegie, M. H., & Celermajer, D. S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00669 · Cited by 46 · see citing works
An insight into the in vivo imaging potential of curcumin analogues as fluorescence probes
Liu, Y., Zhang, C., Pan, H., Li, L., Yu, Y., & Liu, B. (2020) · Asian Journal of Pharmaceutical Sciences · doi:10.1016/j.ajps.2020.11.003 · Cited by 46 · see citing works
Sullivan, S. E., Dillon, G. M., Sullivan, J. M., & Ho, A. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.541003 · Cited by 44 · see citing works
β-amyloid and Oxidative Stress: Perspectives in Drug Development
Caruso, G., Spampinato, S. F., Cardaci, V., Caraci, F., Sortino, M. A., & Merlo, S. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666191209115431 · Cited by 45 · see citing works
Trujillo‐Estrada, L., Jiménez, S., Castro, V. D., Torres, M., Baglietto‐Vargas, D., Moreno‐González, I., Navarro, V., Sanchez-Varo, R. M., Sánchez‐Mejías, E., Dávila, J. C., et al. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-73 · Cited by 43 · see citing works
Bioorthogonal chemical labeling of endogenous neurotransmitter receptors in living mouse brains
Nonaka, H., Sakamoto, S., Shiraiwa, K., Ishikawa, M., Tamura, T., Okuno, K., Kondo, T., Kiyonaka, S., Susaki, E. A., Shimizu, C., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2313887121 · Cited by 43 · see citing works
Cyclin dependent kinase 5: A novel avenue for Alzheimer’s disease
Bhounsule, A. S., Bhatt, L. K., Prabhavalkar, K. S., & Oza, M. J. (2017) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2017.05.006 · Cited by 43 · see citing works
Boonruamkaew, P., Chonpathompikunlert, P., Vong, L. B., Sakaue, S., Tomidokoro, Y., Ishii, K., Tamaoka, A., & Nagasaki, Y. (2017) · Scientific Reports · doi:10.1038/s41598-017-03411-7 · Cited by 43 · see citing works
Hafez, H. A., Kamel, M. A. E.-N., Osman, M. Y. H., Osman, H., Elblehi, S. S., & Mahmoud, S. A. (2021) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-021-04079-4 · Cited by 42 · see citing works
O'Farrell, K., Fagan, E., Connor, T., & Harkin, A. (2017) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2017.07.008 · Cited by 38 · see citing works
Alsharif, I., Boukhzar, L., Lefranc, B., Godefroy, D., Aury‐Landas, J., do Rego, J. L., do-Rego, J.-C., Naudet, F., Arabo, A., Chagraoui, A., et al. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101839 · Cited by 40 · see citing works
Kruk-Słomka, M., Boguszewska‐Czubara, A., Słomka, T., Budzyńska, B., & Biała, G. (2015) · Neural Plasticity · doi:10.1155/2016/9815092 · Cited by 37 · see citing works
Ouyang, Y., Chen, Z., Tan, M., Liu, A., Chen, M., Liu, J., Pi, R., & Fang, J. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.10.160 · Cited by 36 · see citing works
Lentivirus-Mediated HDAC3 Inhibition Attenuates Oxidative Stress in APPswe/PS1dE9 Mice
Yu, L.-J., Liu, Y., Jin, Y., Cao, X., Chen, J., Jin, J.-L., Gu, Y., Bao, X.-Y., Ren, Z., Xu, Y., et al. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-170844 · Cited by 36 · see citing works
Lv, G., Shen, Y., Zheng, W., Yang, J., Li, C., & Lin, J. (2019) · Advanced Therapeutics · doi:10.1002/adtp.201900054 · Cited by 34 · see citing works
Sabaani, N. A. A. (2020) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2019.0151 · Cited by 34 · see citing works
Wan, T., Fu, M., Jiang, Y., Jiang, W., Li, P., & Zhou, S. (2021) · Neurochemical Research · doi:10.1007/s11064-021-03448-1 · Cited by 37 · see citing works
Organic silicon protects human neuroblastoma SH-SY5Y cells against hydrogen peroxide effects
Garcimartín, A., Merino, J. J., González, M. P., Sánchez-Reus, M. I., Sánchez-Muniz, F. J., Bastida, S., & Benedı́, J. (2014) · BMC Complementary and Alternative Medicine · doi:10.1186/1472-6882-14-384 · Cited by 34 · see citing works
Free Heme and Amyloid-β: A Fatal Liaison in Alzheimer’s Disease
Chiziane, E., Telemann, H., Krueger, M. C., Adler, J., Arnhold, J., Alia, A., & Flemmig, J. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170711 · Cited by 33 · see citing works
Neuronal glutathione loss leads to neurodegeneration involving gasdermin activation
Hashimoto, S., Matsuba, Y., Takahashi, M., Kamano, N., Watamura, N., Sasaguri, H., Takado, Y., Yoshihara, Y., Saito, T., & Saido, T. C. (2023) · Scientific Reports · doi:10.1038/s41598-023-27653-w · Cited by 34 · see citing works
Perrotte, M., Page, A. Y. L., Fournet, M., Sayec, M. L., Rassart, É., Fülöp, T., & Ramassamy, C. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.10.452 · Cited by 32 · see citing works
Nopparat, C., Chantadul, V., Permpoonputtana, K., & Govitrapong, P. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.04.001 · Cited by 32 · see citing works
Lactate: elucidating its indispensable role in human health
Zhang, S., Wang, J., Xu, Z., Cheng, Z., Shao, B., & Yu, J. (2026) · Molecular Cancer · doi:10.1186/s12943-025-02519-z · Cited by 35 · see citing works
Byun, J., Son, S. M., Cha, M.-Y., Shong, M., Hwang, Y. J., Kim, Y. S., Ryu, H., Moon, M., Kim, K.-S., & Mook‐Jung, I. (2014) · Cell Death and Differentiation · doi:10.1038/cdd.2014.184 · Cited by 31 · see citing works
Lee, Y. F., Russ, A., Zhao, Q., Perle, S. J., Maci, M., Miller, M. R., Hou, S. S., Algamal, M., Zhao, Z., Li, H., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-40402-3 · Cited by 30 · see citing works
Park, J., Kim, B., Chae, U., Lee, D. G., Kam, M. K., Lee, S., Lee, S., Lee, H., Park, J., & Lee, D. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6810 · Cited by 29 · see citing works
Rodríguez‐Chávez, J. L., Coballase-Urrutía, E., Nieto‐Camacho, A., & Delgado, G. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/843237 · Cited by 28 · see citing works
The Role of Reactive Oxygen Species in Alzheimer's Disease: From Mechanism to Biomaterials Therapy
Yu, Z., & Luo, F. H. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202304373 · Cited by 28 · see citing works
Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits
Yip, J., Chiang, G. S. H., Lee, I. C. J., Lehming-Teo, R., Dai, K., Dongol, L., Wang, L. Y.-T., Teo, D. W. X., Seah, G. T., & Lehming, N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26010364 · Cited by 28 · see citing works
Small Molecules and Alzheimer’s Disease: Misfolding, Metabolism and Imaging
Patel, V., Zhang, X., Tautiva, N., Nyabera, A., Owa, O., Baidya, M., Sung, H., Taunk, P., Abdollahi, S., Charles, S., et al. (2015) · Current Alzheimer Research · doi:10.2174/1567205012666150504145646 · Cited by 25 · see citing works
Therapeutic efficacy of novel memantine nitrate MN-08 in animal models of Alzheimer’s disease
Wu, L., Zhou, X., Cao, Y., MAK, S. H., Zha, L., Li, N., Su, Z., Han, Y., Wang, Y., Man Hoi, M. P., et al. (2021) · Aging Cell · doi:10.1111/acel.13371 · Cited by 24 · see citing works
Fernández, C., Núñez‐Ramírez, R., Jiménez, M., Rivas, G., & Giraldo, R. (2016) · Scientific Reports · doi:10.1038/srep23144 · Cited by 23 · see citing works
Benseny‐Cases, N., Álvarez-Marimon, E., Castillo-Michel, H. A., Cotte, M., Falcon, C., & Cladera, J. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.7b04818 · Cited by 24 · see citing works
Inhibition of Early Upstream Events in Prodromal Alzheimer’s Disease by Use of Targeted Antioxidants
Prasad, K. N., & Bondy, S. C. (2014) · Current Aging Science · doi:10.2174/1874609807666140804115633 · Cited by 24 · see citing works
Li, M., Liu, Z., Ren, J., & Qu, X. (2020) · Chemical Science · doi:10.1039/d0sc01020k · Cited by 20 · see citing works
Li, S., Sun, Y., Gao, Y., Yu, X., Zhao, C., Song, X., Han, F., & Yu, J. H. (2023) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2023.115765 · Cited by 20 · see citing works
Wendt, S., Johnson, S., Weilinger, N. L., Groten, C. J., Sorrentino, S., Frew, J., Yang, L. L. H., Choi, H. B., Nygaard, H. B., & MacVicar, B. A. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102448 · Cited by 16 · see citing works
Weilinger, N. L., Yang, K., Choi, H. B., Groten, C. J., Wendt, S., Murugan, M., Wicki‐Stordeur, L. E., Bernier, L., Velayudhan, P. S., Zheng, J., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113128 · Cited by 18 · see citing works
Kawada, H., & Kador, P. F. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00272 · Cited by 17 · see citing works
Asadbegi, M., Komaki, H., Faraji, N., Azandaryani, M. T., Safari, S., Raoufi, S., Kourosh‐Arami, M., Golipoor, Z., & Komaki, A. (2023) · Psychopharmacology · doi:10.1007/s00213-023-06338-2 · Cited by 17 · see citing works
Redox imaging using genetically encoded redox indicators in zebrafish and mice
Breckwoldt, M. O., Wittmann, C., Misgeld, T., Kerschensteiner, M., & Grabher, C. (2015) · Biological Chemistry · doi:10.1515/hsz-2014-0294 · Cited by 16 · see citing works
Daini, E., Secco, V., Liao, W., Zoli, M., & Vilella, A. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.135869 · Cited by 15 · see citing works
Polajnar, M., Zavašnik‐Bergant, T., Kopitar‐Jerala, N., Tušek‐Žnidarič, M., & Žerovnik, E. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.05.018 · Cited by 15 · see citing works
- Authors
- Xie, H., Hou, S., Jiang, J., Sekutowicz, M., Kelly, J., & Bacskai, B. J.
- Affiliations
- Massachusetts General Hospital (US)
- Tsinghua University (CN)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-04-22
- Volume
- 110
- Issue
- 19
- Pages
- 7904-7909
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3651444
- OpenAlex
- W2086831255
- Cited by
- 172
- References
- 29
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 15 · 2023: 11 · 2022: 12 · 2021: 14 · 2020: 16 · 2019: 17 · 2018: 11 · 2017: 8 · 2016: 11 · 2015: 13 · 2014: 14 · 2013: 8
- FWCI
- 10.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG024688, R01AG024688)
- National Institute of Biomedical Imaging and Bioengineering (EB 000768, R01EB000768)
- National Center for Research Resources (S10RR025645)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid plaques, oxidative stress, neuronal cell death, presenilin 1, amyloid precursor protein, caspase activation, neurodegeneration, neuroprotection
- MeSH terms
- Alzheimer Disease, Animals, Atrophy, Gene Expression Regulation, Image Processing, Computer-Assisted, Mice, Transgenic, Neurons, Oxidation-Reduction, Time Factors, Cell Death, Oxidative Stress, Caspases, Green Fluorescent Proteins, Mice, Plaque, Amyloid
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