Activation of c-Jun N-Terminal Kinase and p38 in an Alzheimer's Disease Model Is Associated with Amyloid Deposition

Savage, Mary J.; Lin, Yin-Guo; Ciallella, John R.; Flood, Dorothy G.; Scott, Richard W.

doi:10.1523/jneurosci.22-09-03376.2002

Cited by 291Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Activation of c-Jun N-Terminal Kinase and p38 in an Alzheimer's Disease Model Is Associated with Amyloid Deposition

Open access

Savage, Mary J., Lin, Yin-Guo, Ciallella, John R., Flood, Dorothy G., Scott, Richard W.·2002·The Journal of Neuroscience

DOI 10.1523/jneurosci.22-09-03376.2002PMC PMC6758401

Open this paper in CoChat — free account Open PDF

Abstract

The mechanisms by which neurons and synapses are lost in Alzheimer's disease (AD) are not completely understood. To characterize potential signaling events linked to AD pathogenesis, activation-specific antibodies were used to examine mitogen-activated protein kinase (MAPK) kinase pathways at various ages in mice transgenic for human amyloid precursor protein-695 with the Swedish familial AD mutations (Tg2576) and homozygous for a P264L familial AD mutation introduced by targeting of the presenilin-1 gene (PS1(P264L)). Although the c-Jun N-terminal kinase (JNK) and p38 pathways were significantly activated in the cortex at both 7 and 12 months of age, there was no significant activation of the extracellular signal-regulated kinase pathway. MAPK kinase-4, an upstream activator of JNK, was also significantly activated at 7 and 12 months, whereas c-Jun, a downstream effector of JNK-associated apoptotic signaling, was not induced. The lack of c-Jun activation is consistent with the absence of neuronal loss in both cortex and hippocampal CA1 at 12 months. The JNK activation was localized to amyloid deposits, within neurites containing phosphorylated tau. Synaptophysin was quantified biochemically as a measure of synaptic integrity and was significantly reduced in an age-dependent manner in the Tg2576/PS1(P264L) cortex but not in either PS1(P264L) or Tg2576 cortex. Stress-responsive MAP kinase pathways were activated in the brain of the Tg2576/PS1(P264L) AD model, and this activation was coincident with the age-dependent increase in amyloid deposition, tau phosphorylation, and loss of synaptophysin.

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.

Integrity signals

Registry

Crossref · 10.1523/jneurosci.22-09-03376.2002

Cites

60 of 60 references verified0 citation errors · 0 not checkable

Statistics

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.

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?

Key components of the senescence-associated secretory phenotype (SASP) are up-regulated in AD.
“Since p38MAPK is a major regulator of SASP [209], it is not surprising that a number of key components of SASP appear to be up-regulated in AD [210,211].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [211]

Self-check

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

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

Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Mammalian MAP kinase signalling cascades
Chang, L., & Karin, M. (2001) · Nature · doi:10.1038/35065000 · Cited by 5,118 · see citing works
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514 · see citing works
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210 · see citing works
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498 · see citing works
Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation
Kyriakis, J. M., & Avruch, J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.807 · Cited by 3,369 · see citing works
Secreted amyloid β–protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599 · see citing works
High-Level Neuronal Expression of Aβ1–42in Wild-Type Human Amyloid Protein Precursor Transgenic Mice: Synaptotoxicity without Plaque Formation
Mucke, L., Masliah, E., Yu, G.-Q., Mallory, M., Rockenstein, E. M., Tatsuno, G., Hu, K., Kholodenko, D., Johnson-Wood, K., & McConlogue, L. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-11-04050.2000 · Cited by 1,856 · see citing works
Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease
Gómez‐Isla, T., Hollister, R., West, H., Mui, S., Growdon, J. H., Petersen, R. C., Parisi, J. E., & Hyman, B. T. (1997) · Annals of Neurology · doi:10.1002/ana.410410106 · Cited by 1,489 · see citing works
Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease
West, M. J., Coleman, P. D., Flood, D. G., & Troncoso, J. C. (1994) · The Lancet · doi:10.1016/s0140-6736(94)92338-8 · Cited by 1,267 · cited 2× · see citing works
“The memory impairments in Alzheimer’s disease (AD) are attributable to the loss of both neurons and synapses (West et al., 1994; DeKosky et al., 1996; Gomez-Isla et al., 1997).”
BackgroundSelf-citation
Unbiased stereological estimation of the number of neurons in the human hippocampus
West, M. J., & Gundersen, H. J. G. (1990) · Journal of Comparative Neurology · doi:10.1002/cne.902960102 · Cited by 1,153 · cited 1× · see citing works
“Neurons were counted with the CASTGrid System (Olympus Optical, Denmark, Copenhagen) using the optical dissector technique (West and Gundersen, 1990).”
Method
Plaque-independent disruption of neural circuits in Alzheimer’s disease mouse models
Hsia, A. Y., Masliah, E., McConlogue, L., Yu, G.-Q., Tatsuno, G., Hu, K., Kholodenko, D., Malenka, R. C., Nicoll, R. A., & Mucke, L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3228 · Cited by 1,123 · see citing works
Cross Talk between ERK and PKA Is Required for Ca2+ Stimulation of CREB-Dependent Transcription and ERK Nuclear Translocation
Impey, S., Obrietan, K. H., Wong, S. T., Poser, S., Yano, S., Wayman, G. A., Deloulme, J., Chan, G. C. ‐., & Storm, D. R. (1998) · Neuron · doi:10.1016/s0896-6273(00)80602-9 · Cited by 889 · see citing works
A Requirement for the Mitogen-activated Protein Kinase Cascade in Hippocampal Long Term Potentiation
English, J. D., & Sweatt, J. D. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.31.19103 · Cited by 860 · see citing works
Early Phenotypic Changes in Transgenic Mice That Overexpress Different Mutants of Amyloid Precursor Protein in Brain
Moechars, D., Dewachter, I., Lorent, K., Reversé, D., Baekelandt, V., Naidu, A., Tesseur, I., Spittaels, K., Haute, C. V. D., Checler, F., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.10.6483 · Cited by 668 · see citing works
Neuron loss in APP transgenic mice
Calhoun, M. E., Wiederhold, K.-H., Abramowski, D., Phinney, A. L., Probst, A., Sturchler-Pierrat, C., Staufenbiel, M., Sommer, B., & Jucker, M. (1998) · Nature · doi:10.1038/27351 · Cited by 502 · see citing works
β-Amyloid Induces Neuronal Apoptosis Via a Mechanism that Involves the c-Jun N-Terminal Kinase Pathway and the Induction of Fas Ligand
MORISHIMA, Y., Gotoh, Y., Zieg, J., Barrett, T., Takano, H., Flavell, R. A., Davis, R. J., Shirasaki, Y., & Greenberg, M. E. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-19-07551.2001 · Cited by 484 · see citing works
β-Amyloid Activates the Mitogen-Activated Protein Kinase Cascade via Hippocampal α7 Nicotinic Acetylcholine Receptors:In VitroandIn VivoMechanisms Related to Alzheimer's Disease
Dineley, K. T., Westerman, M., Bui, D., Bell, K., Ashe, K. H., & Sweatt, J. D. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-12-04125.2001 · Cited by 462 · see citing works
Activation and redistribution of c‐Jun N‐terminal kinase/stress activated protein kinase in degenerating neurons in Alzheimer's disease
Zhu, X.-W., Raina, A., Rottkamp, C., Aliev, G., Perry, G., Boux, H., & Smith, M. A. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00046.x · Cited by 440 · see citing works
Structural Correlates of Cognition in Dementia: Quantification and Assessment of Synapse Change
DeKosky, S. T., Scheff, S. W., & Styren, S. D. (1996) · Neurodegeneration · doi:10.1006/neur.1996.0056 · Cited by 405 · see citing works
DNA damage and apoptosis in Alzheimer's disease: colocalization with c- Jun immunoreactivity, relationship to brain area, and effect of postmortem delay
Anderson, A., Su, J., & Cotman, C. W. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-05-01710.1996 · Cited by 389 · see citing works
Activation of p38 Kinase Links Tau Phosphorylation, Oxidative Stress, and Cell Cycle-Related Events in Alzheimer Disease
Zhu, X., Rottkamp, C. A., Boux, H., Takeda, A., Perry, G., & Smith, M. A. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.10.880 · Cited by 378 · see citing works
p38 Kinase Is Activated in the Alzheimer's Disease Brain
Hensley, K., Floyd, R. A., Zheng, N., Nael, R., Robinson, K. A., Nguyen, X., Pye, Q. N., Stewart, C. A., Geddes, J., Markesbery, W. R., et al. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0722053.x · Cited by 373 · see citing works
Phosphorylation Sites on Tau Identified by Nanoelectrospray Mass Spectrometry
Reynolds, C. H., Betts, J. C., Blackstock, W. P., Nebreda, Á. R., & Anderton, B. H. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0741587.x · Cited by 365 · see citing works
Microtubule-interfering Agents Activate c-Jun N-terminal Kinase/Stress-activated Protein Kinase through Both Ras and Apoptosis Signal-regulating Kinase Pathways
Wang, T., Wang, H.-S., Ichijo, H., Giannakakou, P., Foster, J. S., Fojo, T., & Wimalasena, J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.9.4928 · Cited by 353 · see citing works
Lasting N-Terminal Phosphorylation of c-Jun and Activation of c-Jun N-Terminal Kinases after Neuronal Injury
Herdegen, T., Claret, F.-X., Kallunki, T., Martín-Villalba, A., Winter, C., Hunter, T., & Karin, M. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-14-05124.1998 · Cited by 327 · see citing works
Phosphorylation of microtubule‐associated protein tau by stress‐activated protein kinases
Goedert, M., Hasegawa, M., Jakes, R., Lawler, S., Cuenda, A., & Cohen, P. R. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00483-3 · Cited by 308 · see citing works
Activation of neuronal extracellular receptor kinase (ERK) in Alzheimer disease links oxidative stress to abnormal phosphorylation.
Perry, G., Roder, H., Nunomura, A., Takeda, A., Friedlich, A., Zhu, X.-W., Raina, A., Holbrook, N., Siedlak, S., Harris, P., et al. (1999) · NeuroReport · doi:10.1097/00001756-199908020-00035 · Cited by 296 · see citing works
Mutations of the presenilin I gene in families with early-onset Alzheimer's disease
Campion, D., Flaman, J., Brice, A., Hannequin, D., Dubois, B., Martin, C., Moreau, V., Charbonnier, F., Didierjean, O., Tardieu, S., et al. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.12.2373 · Cited by 277 · see citing works
β-Amyloid Fibrils Activate Parallel Mitogen-Activated Protein Kinase Pathways in Microglia and THP1 Monocytes
McDonald, D. R., Bamberger, M. E., Combs, C. K., & Landreth, G. E. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-12-04451.1998 · Cited by 259 · see citing works
Phosphorylated Map Kinase (ERK1, ERK2) Expression is Associated with Early Tau Deposition in Neurones and Glial Cells, but not with Increased Nuclear DNA Vulnerability and Cell Death, in Alzheimer Disease, Pick's Disease, Progressive Supranuclear Palsy and Corticobasal Degeneration
Ferrer, I., Blanco, R., Carmona, M., Ribera, R., Goutan, E., Puig, B., Rey, M. J., Cardozo, A., Viñals, F., & Ribalta, T. (2001) · Brain Pathology · doi:10.1111/j.1750-3639.2001.tb00387.x · Cited by 239 · see citing works
Peripheral Axotomy Induces Long-Term c-Jun Amino-Terminal Kinase-1 Activation and Activator Protein-1 Binding Activity by c-Jun and junD in Adult Rat Dorsal Root GangliaIn Vivo
Kenney, A. M., & Kocsis, J. D. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-04-01318.1998 · Cited by 234 · see citing works
beta-Amyloid-induced neuronal apoptosis requires c-Jun N-terminal kinase activation
Troy, C. M., Rabacchi, S. A., Xu, Z., Maroney, A. C., Connors, T. J., Shelanski, M. L., & Greene, L. A. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.t01-1-00218.x · Cited by 223 · see citing works
Mitogen-activated protein kinases activated by lipopolysaccharide and β-amyloid in cultured rat microglia
Pyo, H., Jou, I., Jung, S., Hong, S., & Joe, E.-H. (1998) · Neuroreport · doi:10.1097/00001756-199803300-00020 · Cited by 217 · see citing works
Inhibition of Protein Phosphatase 2A Overrides Tau Protein Kinase I/Glycogen Synthase Kinase 3β and Cyclin-dependent Kinase 5 Inhibition and Results in Tau Hyperphosphorylation in the Hippocampus of Starved Mouse
Planel, E., Yasutake, K., Fujita, S. C., & Ishiguro, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102780200 · Cited by 197 · see citing works
Reorganization of cholinergic terminals in the cerebral cortex and hippocampus in transgenic mice carrying mutated presenilin-1 and amyloid precursor protein transgenes
Wong, T. P., Debeir, T., Duff, K., & Cuello, A. C. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-07-02706.1999 · Cited by 196 · see citing works
Dual Roles for c-Jun N-Terminal Kinase in Developmental and Stress Responses in Cerebellar Granule Neurons
Coffey, E. T., Hongisto, V., Dickens, M., Davis, R. J., & Courtney, M. J. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-20-07602.2000 · Cited by 191 · see citing works
CEP‐1347 (KT7515), an Inhibitor of JNK Activation, Rescues Sympathetic Neurons and Neuronally Differentiated PC12 Cells from Death Evoked by three Distinct Insults
Maroney, A. C., Finn, J. P., Bozyczko‐Coyne, D., O’Kane, T. M., Neff, N. T., Tolkovsky, A. M., Park, D. S., Yan, C. Y. I., Troy, C. M., & Greene, L. A. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.01901.x · Cited by 190 · see citing works
c-Jun N-Terminal Kinase (JNK)-Interacting Protein-1b/Islet-Brain-1 Scaffolds Alzheimer's Amyloid Precursor Protein with JNK
Matsuda, S., Yasukawa, T., Homma, Y., Ito, Y., Niikura, T., Hiraki, T., Hirai, S., Ohno, S., Kita, Y. A., Kawasumi, M., et al. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-17-06597.2001 · Cited by 184 · see citing works
Activation of the JNK/p38 Pathway Occurs in Diseases Characterized by Tau Protein Pathology and Is Related to Tau Phosphorylation But Not to Apoptosis
Atzori, C., Ghetti, B. F., Piva, R., Srinivasan, A., Zolo, P., Delisle, M. B., Mirra, S. S., & Migheli, A. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.12.1190 · Cited by 175 · see citing works
Increased Immunoreactivity for Jun- and Fos-Related Proteins in Alzheimer's Disease: Association with Pathology
Anderson, A. J., Cummings, B. J., & Cotman, C. W. (1994) · Experimental Neurology · doi:10.1006/exnr.1994.1031 · Cited by 174 · see citing works
Hemopoietic Growth Factors with the Exception of Interleukin-4 Activate the p38 Mitogen-activated Protein Kinase Pathway
Foltz, I. N., Lee, J. C., Young, P. R., & Schrader, J. W. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.6.3296 · Cited by 169 · see citing works
Pathogenic Mechanisms of Alzheimer's Disease Analyzed in the APP23 Transgenic Mouse Model
Sturchler, C., & Staufenbiel, M. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06915.x · 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
Activation of MKK6, an upstream activator of p38, in Alzheimer's disease
Zhu, X.-W., Rottkamp, C., Hartzler, A., Sun, Z., Takeda, A., Boux, H., Shimohama, S., Perry, G., & Smith, M. A. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00597.x · Cited by 151 · see citing works
CEP‐1347/KT‐7515, an inhibitor of SAPK/JNK pathway activation, promotes survival and blocks multiple events associated with Aβ‐induced cortical neuron apoptosis
Bozyczko‐Coyne, D., O’Kane, T. M., Wu, Z.-L., Dobrzański, P., Murthy, S., Vaught, J. L., & Scott, R. W. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00294.x · Cited by 151 · see citing works
Self-citation
Structure, Microtubule Interactions, and Phosphorylation of Tau Proteina
Mandelkow�, E., Schweers, O., Drewes, G., Biernat, J., Gustke, N., Trinczek, B., & Mandelkow, E. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb34407.x · Cited by 142 · see citing works
Presenilin-1 P264L Knock-In Mutation: Differential Effects on Aβ Production, Amyloid Deposition, and Neuronal Vulnerability
Siman, R., Reaume, A. G., Savage, M. J., Trusko, S., Lin, Y.-G., Scott, R. W., & Flood, D. G. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-23-08717.2000 · Cited by 133 · see citing works
Self-citation
FAD mutant PS-1 gene-targeted mice: increased Aβ42 and Aβ deposition without APP overproduction
Flood, D. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00330-x · Cited by 131 · see citing works
Self-citation
Dishevelled Regulates the Metabolism of Amyloid Precursor Protein via Protein Kinase C/Mitogen-Activated Protein Kinase and c-Jun Terminal Kinase
Mudher, A. K., Chapman, S. C., Richardson, J. C., Asuni, A. A., Gibb, G., Pollard, C. C., Killick, R., Iqbal, T. A., Raymond, F. L., Varndell, I. M., et al. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-14-04987.2001 · Cited by 122 · see citing works
Phosphorylation of thr668in the cytoplasmic domain of the Alzheimer's disease amyloid precursor protein by stress‐activated protein kinase 1b (Jun N‐terminal kinase‐3)
Standen, C. L., Brownlees, J., Grierson, A. J., Kesavapany, S., Lau, K., McLoughlin, D. M., & Miller, C. C. J. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00102.x · Cited by 121 · see citing works
Neurofibrillary Pathology in Transgenic Mice Overexpressing V717F β-Amyloid Precursor Protein
Masliah, E., Sisk, A., Mallory, M. E., & Games, D. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.4.357 · Cited by 117 · see citing works
Familial Alzheimer's chromosome 14 mutations
Wasco, W., Pettingell, W. P., Jondro, P. D., Schmidt, S. D., Gurubhagavatula, S., Rodes, L., Di-Blasi, T., Romano, D., Guénette, S. Y., Kovacs, D. M., et al. (1995) · Nature Medicine · doi:10.1038/nm0995-848a · Cited by 109 · see citing works
Plasma Levels of amyloid β proteins Aβ1–40 and Aβ1–42(43) are elevated in Down's syndrome
Tokuda, T., Fukushima, T., Ikeda, S., Sekijima, Y., Shoji, S., Yanagisawa, N., & Tamaoka, A. (1997) · Annals of Neurology · doi:10.1002/ana.410410220 · Cited by 92 · see citing works
Cathepsin G: Localization in human cerebral cortex and generation of amyloidogenic fragments from the β-amyloid precursor protein
Savage, M. J., Iqbal, M., Loh, T., Trusko, S. P., Scott, R. W., & Siman, R. (1994) · Neuroscience · doi:10.1016/0306-4522(94)90490-1 · Cited by 56 · see citing works
Self-citation
Brain Aβ amyloidosis in APPsw mice induces accumulation of presenilin-1 and tau
Tomidokoro, Y., Harigaya, Y., Matsubara, E., Ikeda, M., Kawarabayashi, T., Shirao, T., Ishiguro, K., Okamoto, K., Younkin, S. G., & Shoji, M. (2001) · The Journal of Pathology · doi:10.1002/path.897 · Cited by 53 · see citing works
CEP-1347/KT7515, a JNK pathway inhibitor, supports the in vitro survival of chick embryonic neurons
Borasio, G. D., Horstmann, S., Anneser, J. M. H., Neff, N. T., & Glicksman, M. A. (1998) · Neuroreport · doi:10.1097/00001756-199805110-00034 · Cited by 44 · see citing works
Molecular Mechanism of Alzheimer's Neurofibrillary Degeneration and Therapeutic Interventiona
Iqbal, K., & Grundke, I. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb34411.x · Cited by 38 · see citing works
Negative Regulation of the Sapk/Jnk Signaling Pathway by Presenilin 1
Kim, J. W., Chang, T.-S., Lee, J. E., Huh, S., Yeon, S. W., Yang, W. S., Joe, C. O., Mook‐Jung, I., Tanzi, R. E., Kim, T., et al. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.153.3.457 · Cited by 29 · see citing works
Topographic organization of connections between the hypothalamus and prefrontal cortex in the rhesus monkey
Rempel-Clower, N. L., & Barbas, H. (1998) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19980831)398:3
Self-citation

Flagged first, then by citations

1 of the 61 references couldn’t be matched to a known paper.

Sorted by citations

Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution
Stefani, M., & Dobson, C. M. (2003) · Journal of Molecular Medicine · doi:10.1007/s00109-003-0464-5 · Cited by 1,643 · see citing works
Lipopolysaccharide-Induced Inflammation Exacerbates Tau Pathology by a Cyclin-Dependent Kinase 5-Mediated Pathway in a Transgenic Model of Alzheimer's Disease
Kitazawa, M., Oddo, S., Yamasaki, T. R., Green, K. N., & LaFerla, F. M. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2868-05.2005 · Cited by 697 · see citing works
CD14 and Toll-Like Receptors 2 and 4 Are Required for Fibrillar Aβ-Stimulated Microglial Activation
Reed-Geaghan, E. G., Savage, J. C., Hise, A. G., & Landreth, G. E. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3158-09.2009 · Cited by 591 · see citing works
Neuropathology and Pathogenesis of Encephalitis following Amyloid β Immunization in Alzheimer's Disease
Ferrer, I., Boada, M., Guerra, M. L. S., Rey, M. J., & Costa‐Jussà, F. R. (2004) · Brain Pathology · doi:10.1111/j.1750-3639.2004.tb00493.x · Cited by 567 · see citing works
-Amyloid Oligomers Induce Phosphorylation of Tau and Inactivation of Insulin Receptor Substrate via c-Jun N-Terminal Kinase Signaling: Suppression by Omega-3 Fatty Acids and Curcumin
Ma, Q.-L., Yang, F., Rosario, E. R., Ubeda, O. J., Beech, W., Gant, D. J., Chen, P. P., Hudspeth, B., Chen, C., Zhao, Y., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1071-09.2009 · Cited by 536 · see citing works
Ageing, Cellular Senescence and Neurodegenerative Disease
Kritsilis, M., V. Rizou, S., Koutsoudaki, P. N., Evangelou, K., Gorgoulis, V. G., & Papadopoulos, D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19102937 · Cited by 448 · see citing works
“Since p38MAPK is a major regulator of SASP [209], it is not surprising that a number of key components of SASP appear to be up-regulated in AD [210,211].”
Background
Block of Long-Term Potentiation by Naturally Secreted and Synthetic Amyloid β-Peptide in Hippocampal Slices Is Mediated via Activation of the Kinases c-Jun N-Terminal Kinase, Cyclin-Dependent Kinase 5, and p38 Mitogen-Activated Protein Kinase as well as Metabotropic Glutamate Receptor Type 5
Wang, Q., Walsh, D. M., Rowan, M. J., Selkoe, D. J., & Anwyl, R. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1633-03.2004 · Cited by 437 · see citing works
c-Jun N-terminal Kinase (JNK) Signaling as a Therapeutic Target for Alzheimer’s Disease
Yarza, R., Vela, S., Solas, M., & Ramírez, M. J. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00321 · Cited by 418 · see citing works
The Role of Mitogen-Activated Protein Kinase Pathways in Alzheimer’s Disease
Zhu, X., Lee, H., Raina, A. K., Perry, G. L., & Smith, M. A. (2002) · Neurosignals · doi:10.1159/000067426 · Cited by 392 · see citing works
Oxidative stress signalling in Alzheimer's disease
Zhu, X., Raina, A. K., Lee, H., Casadesús, G., Smith, M. A., & Perry, G. L. (2004) · Brain Research · doi:10.1016/j.brainres.2004.01.012 · Cited by 390 · see citing works
Tumor Necrosis Factor-α, Interleukin-1β, and Interferon-γ Stimulate γ-Secretase-mediated Cleavage of Amyloid Precursor Protein through a JNK-dependent MAPK Pathway
Liao, Y.-F., Wang, B.-J., Cheng, H.-T., Kuo, L.-H., & Wolfe, M. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402034200 · Cited by 389 · see citing works
Role of Redox Signaling in Neuroinflammation and Neurodegenerative Diseases
Hsieh, H., & Yang, C. (2013) · BioMed Research International · doi:10.1155/2013/484613 · Cited by 370 · see citing works
Inflammation in Alzheimer's disease: Amyloid-β oligomers trigger innate immunity defence via pattern recognition receptors
Salminen, A., Ojala, J. O., Kauppinen, A., Kaarniranta, K., & Suuronen, T. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.01.001 · Cited by 350 · see citing works
Oxidative Stress Signaling in Alzheimers Disease
Su, B., Wang, X., Nunomura, A., Moreira, P., Lee, H.-G., Perry, G., Smith, M., & Zhu, X. (2008) · Current Alzheimer Research · doi:10.2174/156720508786898451 · Cited by 344 · see citing works
Nuclear and cytosolic JNK signalling in neurons
Coffey, E. T. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3729 · Cited by 336 · see citing works
RAGE‐dependent signaling in microglia contributes to neuroinflammation, Aβ accumulation, and impaired learning/memory in a mouse model of Alzheimer's disease
Fang, F., Lue, L.-F., Yan, S., Xu, H., Luddy, J. S., Chen, D., Walker, D. G., Stern, D. M., Yan, S., Schmidt, A. M., et al. (2010) · The FASEB Journal · doi:10.1096/fj.09-139634 · Cited by 335 · 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
Current Advances on Different Kinases Involved in Tau Phosphorylation, and Implications in Alzheimers Disease and Tauopathies
Ferrer, I., Gómez‐Isla, T., Puig, B., Freixes, M., Ribé, E. M., Dalfó, E., & Ávila, J. (2005) · Current Alzheimer Research · doi:10.2174/1567205052772713 · Cited by 302 · see citing works
Shaping the Nrf2-ARE-related pathways in Alzheimer’s and Parkinson’s diseases
Fão, L., Mota, S. I., & Rego, A. C. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100942 · Cited by 270 · see citing works
The Role of p38 MAPK and Its Substrates in Neuronal Plasticity and Neurodegenerative Disease
Corrêa, S. A. L., & Eales, K. L. (2012) · Journal of Signal Transduction · doi:10.1155/2012/649079 · Cited by 258 · see citing works
Importance of MAPK pathways for microglial pro-inflammatory cytokine IL-1β production
Kim, S. H., Smith, C. J., & Eldik, L. J. V. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(03)00126-x · Cited by 234 · see citing works
A novel p38α MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model
Munoz, L., Ranaivo, H. R., Roy, S. M., Hu, W., Craft, J. M., McNamara, L. K., Chico, L. W., Van Eldik, L. J., & Watterson, D. M. (2007) · Journal of Neuroinflammation · doi:10.1186/1742-2094-4-21 · Cited by 224 · see citing works
JNK Signalling: A Possible Target to Prevent Neurodegeneration
Borsello, T., & Forloni, G. (2007) · Current Pharmaceutical Design · doi:10.2174/138161207780858384 · Cited by 224 · see citing works
P38 MAP kinase is activated at early stages in Alzheimer's disease brain
Sun, A. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00180-8 · Cited by 219 · see citing works
Treadmill exercise represses neuronal cell death in an aged transgenic mouse model of Alzheimer's disease
Um, H.-S., Kang, E., Koo, J., Kim, H.-T., Jin-Lee, Kim, E.-J., Yang, C., An, G.-Y., Cho, I., & Cho, J. (2010) · Neuroscience Research · doi:10.1016/j.neures.2010.10.004 · Cited by 212 · 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
“Pre1197 treatment of these NT2 cells with -tocopherol 1198 prevented BACE induction and CTF generation 1199 demonstrating direct involvement of oxidative stress 1200 in inducing BACE activity [81, 297].”
Background
Loss of α7 Nicotinic Receptors Enhances β-Amyloid Oligomer Accumulation, Exacerbating Early-Stage Cognitive Decline and Septohippocampal Pathology in a Mouse Model of Alzheimer's Disease
Hernandez, C. M., Kayed, R., Zheng, H., Sweatt, J. D., & Dineley, K. T. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5038-09.2010 · Cited by 204 · see citing works
“Previous studies on APP mice have failed to detect robust deficits in synaptophysin at any age, and MAP2 decline has only been reported for aged APP animals (9 –24 months old) (Savage et al., 2002; Fonseca et al., 2004).”
Background
JNK pathway: diseases and therapeutic potential
Cui, J., Zhang, M., Zhang, Y., & Xu, Z. (2007) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2007.00579.x · Cited by 202 · see citing works
Neurotoxic Mechanisms Caused by the Alzheimer's Disease-linked Swedish Amyloid Precursor Protein Mutation
Marques, C. A., Keil, U., Bonert, A., Steiner, B., Haass, C., Müller, W. E., & Eckert, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212265200 · Cited by 175 · see citing works
Essential Role of E2-25K/Hip-2 in Mediating Amyloid-β Neurotoxicity
Song, S., Kim, S., Hong, Y., Jo, D., Lee, J., Shim, S. M., Chung, C., Seo, S. J., Yoo, Y. J., Koh, J., et al. (2003) · Molecular Cell · doi:10.1016/j.molcel.2003.08.005 · Cited by 167 · see citing works
Sleep and circadian abnormalities in a transgenic mouse model of Alzheimer’s disease: A role for cholinergic transmission
Wisor, J. P., Edgar, D. M., Yesavage, J. A., Ryan, H. S., McCormick, C. M., Lapustea, N., & Murphy, G. M. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2004.11.018 · Cited by 169 · see citing works
Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer transgenic mouse model
Wang, X., Zheng, W. H., Xie, J., Wang, T., Wang, S., Teng, W., & Wang, Z. (2010) · Molecular Neurodegeneration · doi:10.1186/1750-1326-5-46 · Cited by 161 · see citing works
Ras and Rap Signaling in Synaptic Plasticity and Mental Disorders
Stornetta, R. L., & Zhu, J. (2010) · The Neuroscientist · doi:10.1177/1073858410365562 · Cited by 159 · see citing works
Increased MAP kinase activity in Alzheimer's and Down syndrome but not in schizophrenia human brain
SWATTON, J. E., Sellers, L. A., Faull, R. L. M., Holland, A. J., Iritani, S., & Bahn, S. (2004) · European Journal of Neuroscience · doi:10.1111/j.0953-816x.2004.03365.x · Cited by 158 · see citing works
Activation of the ERK and JNK signaling pathways caused by neuron-specific inhibition of PP2A in transgenic mice
Kins, S., Kurosinski, P., Nitsch, R. M., & Götz, J. (2003) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63444-x · Cited by 155 · see citing works
The p38 MAP Kinase Family as Regulators of Proinflammatory Cytokine Production in Degenerative Diseases of the CNS.
Bachstetter, A. D., & Eldik, L. J. V. (2010) · PubMed Central · Cited by 155 · see citing works
Cellular Signaling Mechanisms for Muscarinic Acetylcholine Receptors
Lanzafame, A. A., Christopoulos, A., & Mitchelson, F. J. (2003) · Receptors and Channels · doi:10.3109/10606820308263 · Cited by 147 · see citing works
Tyk2/STAT3 Signaling Mediates β-Amyloid-Induced Neuronal Cell Death: Implications in Alzheimer's Disease
Wan, J., Fu, A. K. Y., Ip, F. C. F., Ng, H., Hugon, J., Page, G., Wang, J. H.-C., Lai, K., Wu, Z., & Ip, N. Y. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0519-10.2010 · Cited by 143 · see citing works
Glia Proinflammatory Cytokine Upregulation as a Therapeutic Target for Neurodegenerative Diseases: Function‐Based and Target‐Based Discovery Approaches
Eldik, L. J. V., Thompson, W. L., Ranaivo, H. R., Behanna, H. A., & Watterson, D. M. (2007) · International review of neurobiology · doi:10.1016/s0074-7742(07)82015-0 · Cited by 141 · see citing works
Role of Hydrogen Peroxide in the Aetiology of Alzheimer??s Disease
Milton, N. G. N. (2004) · Drugs & Aging · doi:10.2165/00002512-200421020-00002 · Cited by 141 · see citing works
Insulin Resistance at the Crossroad of Alzheimer Disease Pathology: A Review
Berlanga‐Acosta, J., Guillén, G. E., Rodríguez-Rodríguez, N., Bringas-Vega, M. L., García-del-Barco-Herrera, D., Berlanga-Saez, J. O., Ojalvo, A. G., Valdés-Sosa, M. J., & Valdes-Sosa, P. A. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.560375 · Cited by 139 · see citing works
FoxO3a is activated and executes neuron death via Bim in response to β-amyloid
Sanphui, P., & Biswas, S. C. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.148 · Cited by 137 · see citing works
Promising therapeutic potential of pterostilbene and its mechanistic insight based on preclinical evidence
Kosuru, R., Rai, U., Prakash, S., Singh, A., & Singh, S. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.07.046 · Cited by 137 · see citing works
Molecular mechanisms linking amyloid β toxicity and Tau hyperphosphorylation in Alzheimer׳s disease
Lloret, A., Fuchsberger, T., Giraldo, E., & Viña, J. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.02.028 · Cited by 135 · see citing works
Protection by EGb 761 against β-amyloid-induced neurotoxicity: Involvement of NF-κB, SIRT1, and MAPKs pathways and inhibition of amyloid fibril formation
Longpré, F., Garneau, P., Christen, Y., & Ramassamy, C. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.08.015 · Cited by 131 · see citing works
Redox regulates COX-2 upregulation and cell death in the neuronal response to cadmium
Rockwell, P. (2003) · Cellular Signalling · doi:10.1016/j.cellsig.2003.08.006 · Cited by 132 · see citing works
Targeting JNK3 for the treatment of neurodegenerative disorders
Resnick, L., & Fennell, M. (2004) · Drug Discovery Today · doi:10.1016/s1359-6446(04)03251-9 · Cited by 128 · see citing works
β-Amyloid-induced Dynamin 1 Depletion in Hippocampal Neurons
Kelly, B. L., Vassar, R. J., & Ferreira, A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503259200 · Cited by 127 · see citing works
The role of TNF-α signaling pathway on COX-2 upregulation and cognitive decline induced by β-amyloid peptide
Medeiros, R., Figueiredo, C. P., Pandolfo, P., Duarte, F. S., Prediger, R. D. S., Passos, G. F., & Calixto, J. B. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.01.040 · Cited by 121 · see citing works
Herp Stabilizes Neuronal Ca2+ Homeostasis and Mitochondrial Function during Endoplasmic Reticulum Stress
Chan, S. L., Fu, W., Zhang, P., Cheng, A., Lee, J., Kokame, K., & Mattson, M. P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404272200 · Cited by 118 · see citing works
Activation of the c-Jun N-terminal Kinase Signaling Cascade Mediates the Effect of Amyloid-β on Long Term Potentiation and Cell Death in Hippocampus
Minogue, A. M., Schmid, A. W., Fogarty, M. P., Moore, A. C., Campbell, V. A., Herron, C. E., & Lynch, M. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302530200 · Cited by 117 · see citing works
Are there roles for brain cell senescence in aging and neurodegenerative disorders?
Tan, F. C. C., Hutchison, E. R., Eitan, E., & Mattson, M. P. (2014) · Biogerontology · doi:10.1007/s10522-014-9532-1 · Cited by 116 · see citing works
MKP-1 reduces Aβ generation and alleviates cognitive impairments in Alzheimer’s disease models
Du, Y., Du, Y., Zhang, Y., Huang, Z., Fu, M., Li, J., Pang, Y., Lei, P., Wang, Y. T., Song, W., et al. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0091-4 · Cited by 117 · see citing works
p38 MAP Kinase Inhibitors as Potential Therapeutic Drugs for Neural Diseases
Yasuda, S., Sugiura, H., Tanaka, H., Takigami, S., & Yamagata, K. (2011) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/187152411794961040 · Cited by 112 · see citing works
MAPKs: new targets for neurodegeneration
Harper, S. J., & Wilkie, N. M. (2003) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.7.2.187 · Cited by 111 · see citing works
Vanillic Acid, a Bioactive Phenolic Compound, Counteracts LPS-Induced Neurotoxicity by Regulating c-Jun N-Terminal Kinase in Mouse Brain
Ullah, R., Ikram, M. A., Park, T. J., Ahmad, R., Saeed, K. M., Alam, S. I., Rehman, I. U., Khan, A., Khan, I., Jo, M. G., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010361 · Cited by 112 · see citing works
The p38 MAP kinase signaling pathway in Alzheimer's disease
Johnson, G. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00268-1 · Cited by 106 · see citing works
Inhibition of c‐ J un N ‐terminal kinase activation reverses A lzheimer disease phenotypes in APP swe/ PS 1dE 9 mice
Zhou, Q., Wang, M., Du, Y., Zhang, W., Bai, M., Zhang, Z., Li, Z., & Miao, J. (2015) · Annals of Neurology · doi:10.1002/ana.24361 · Cited by 105 · see citing works
Synergistic Effects of the SAPK/JNK and the Proteasome Pathway on Glial Fibrillary Acidic Protein (GFAP) Accumulation in Alexander Disease
Tang, G., Xu, Z., & Goldman, J. E. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604942200 · Cited by 104 · see citing works
Photobiomodulation by low-power laser irradiation attenuates Aβ-induced cell apoptosis through the Akt/GSK3β/β-catenin pathway
Liang, J., Liu, L., & Xing, D. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.08.003 · Cited by 102 · see citing works
Microglial p38α MAPK is critical for LPS-induced neuron degeneration, through a mechanism involving TNFα
Xing, B., Bachstetter, A. D., & Van Eldik, L. J. (2011) · Molecular Neurodegeneration · doi:10.1186/1750-1326-6-84 · Cited by 101 · see citing works
Hippocampal Injections of Oligomeric Amyloid β-peptide (1–42) Induce Selective Working Memory Deficits and Long-lasting Alterations of ERK Signaling Pathway
Faucher, P., Mons, N., Micheau, J., Louis, C., & Beracochea, D. J. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00245 · Cited by 100 · see citing works
Inhibition of γ-secretase activity reduces Aβ production, reduces oxidative stress, increases mitochondrial activity and leads to reduced vulnerability to apoptosis: Implications for the treatment of Alzheimer's disease
Sheng, B., Gong, K., Niu, Y., Liu, L., Yan, Y., Lu, G., Zhang, L., Hu, M., Zhao, N., Zhang, X., et al. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.02.018 · Cited by 97 · see citing works
Signal Transduction Cascades Associated with Oxidative Stress in Alzheimer's Disease
Petersen, R. B., Nunomura, A., Lee, H., Casadesús, G., Perry, G. L., Smith, M. A., & Zhu, X. (2007) · Journal of Alzheimer s Disease · doi:10.3233/jad-2007-11202 · Cited by 99 · see citing works
Antagonizing β-amyloid peptide neurotoxicity of the anti-aging fungus Ganoderma lucidum
Lai, C. S.-W., Yu, M.-S., Yuen, W.-H., So, K., Zee, S., & Chang, R. C. (2007) · Brain Research · doi:10.1016/j.brainres.2007.10.103 · Cited by 93 · see citing works
VGF-derived peptide TLQP-21 modulates microglial function through C3aR1 signaling pathways and reduces neuropathology in 5xFAD mice
El Gaamouch, F., Audrain, M., Lin, W.-J., Beckmann, N., Jiang, C., Hariharan, S., Heeger, P. S., Schadt, E. E., Gandy, S., Ehrlich, M. E., et al. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-0357-x · Cited by 92 · see citing works
The cell cycle as a therapeutic target for Alzheimer's disease
Neve, R. L., & McPhie, D. L. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.09.005 · Cited by 92 · see citing works
Omega-3 polyunsaturated fatty acids in the brain: metabolism and neuroprotection
Zhang, W. (2011) · Frontiers in bioscience · doi:10.2741/3878 · Cited by 92 · see citing works
Aberrant phosphorylation in the pathogenesis of Alzheimer's disease
Chung, S. (2009) · BMB Reports · doi:10.5483/bmbrep.2009.42.8.467 · Cited by 89 · see citing works
p53-dependent SIRT6 expression protects Aβ42-induced DNA damage
Jung, E. S., Choi, H., Song, H., Hwang, Y. J., Kim, A., Ryu, H., & Mook‐Jung, I. (2016) · Scientific Reports · doi:10.1038/srep25628 · Cited by 90 · see citing works
JNK3 as a Therapeutic Target for Neurodegenerative Diseases
Antoniou, X., Falconi, M., Marino, D. D., & Borsello, T. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-091567 · Cited by 87 · see citing works
Expression of stress‐activated kinases c‐Jun N‐terminal kinase (SAPK/JNK‐P) and p38 kinase (p38‐P), and tau hyperphosphorylation in neurites surrounding βA plaques in APP Tg2576 mice
Puig, B., Gómez‐Isla, T., Ribé, E. M., Cuadrado‐Tejedor, M., Torrejón-Escribano, B., Dalfó, E., & Ferrer, I. (2004) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2004.00569.x · Cited by 85 · see citing works
A transgenic rat model of Alzheimer's disease with extracellular Aβ deposition
Flood, D. G., Lin, Y., Lang, D. M., Trusko, S. P., Hirsch, J. D., Savage, M. J., Scott, R. W., & Howland, D. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.10.006 · Cited by 85 · see citing works
Self-citation
JNK and ERK1/2 pathways have a dual opposite effect on the expression of BACE1
Tamagno, E., Guglielmotto, M., Giliberto, L., Vitali, A., Borghi, R., Autelli, R., Danni, O., & Tabaton, M. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.12.015 · Cited by 84 · see citing works
c-Jun N-terminal Kinase Regulates Soluble Aβ Oligomers and Cognitive Impairment in AD Mouse Model
Sclip, A., Antoniou, X., Colombo, A. V., Camici, G. G., Pozzi, L., Cardinetti, D., Feligioni, M., Veglianese, P., Bahlmann, F. H., Cervo, L., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.297515 · Cited by 84 · see citing works
Neuroprotective strategies in Alzheimer’s disease
Longo, F. M., & Massa, S. M. (2004) · NeuroRx · doi:10.1602/neurorx.1.1.117 · Cited by 83 · see citing works
Comparative analysis of cortical gene expression in mouse models of Alzheimer's disease
Wu, Z., Ciallella, J. R., Flood, D. G., O’Kane, T. M., Bozyczko‐Coyne, D., & Savage, M. J. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.02.010 · Cited by 83 · see citing works
Self-citation
Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer’s Disease
Litwiniuk, A., Bik, W., Kalisz, M., & Baranowska-Bik, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115603 · Cited by 82 · see citing works
Inhibition of c-Jun kinase provides neuroprotection in a model of Alzheimer's disease
Braithwaite, S. P., Schmid, R. S., Dong, H., Sung, M.-L. A., Cho, S., Resnick, L., Monaghan, M. M., Hirst, W. D., Essrich, C., Reinhart, P. H., et al. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.04.015 · Cited by 82 · see citing works
Caffeine induces beneficial changes in PKA signaling and JNK and ERK activities in the striatum and cortex of Alzheimer's transgenic mice
Zeitlin, R., Patel, S., Burgess, S., Arendash, G. W., & Echeverrı́a, V. (2011) · Brain Research · doi:10.1016/j.brainres.2011.08.036 · Cited by 82 · see citing works
Intranasal deferoxamine attenuates synapse loss via up-regulating the P38/HIF-1α pathway on the brain of APP/PS1 transgenic mice
Guo, C., Zhang, Y., Wang, T., Zhong, M., Yang, Z., Hao, L.-J., Chai, R., & Zhang, S. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00104 · Cited by 79 · see citing works
Drug Discovery of DKK1 Inhibitors
Jiang, H., Zhang, Z., Yu, Y., Chu, H. Y., Yu, S., Yao, S., Zhang, G., & Zhang, B. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.847387 · Cited by 79 · see citing works
The regulation of p53 up‐regulated modulator of apoptosis by JNK /c‐Jun pathway in β‐amyloid‐induced neuron death
Akhter, R., Sanphui, P., Das, H., Saha, P., & Biswas, S. C. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13128 · Cited by 78 · see citing works
RETRACTED: 5‐Lipoxygenase gene transfer worsens memory, amyloid, and tau brain pathologies in a mouse model of alzheimer disease
Chu, J., Giannopoulos, P. F., Ceballos‐Diaz, C., Golde, T. E., & Praticò, D. (2012) · Annals of Neurology · doi:10.1002/ana.23642 · Cited by 77 · see citing works
Retracted
p38 MAP kinase-mediated NMDA receptor-dependent suppression of hippocampal hypersynchronicity in a mouse model of Alzheimer’s disease
Ittner, A., Gladbach, A., Bertz, J., Suh, L. S., & Ittner, L. M. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0149-z · Cited by 77 · see citing works
Green tea catechin leads to global improvement among Alzheimer's disease-related phenotypes in NSE/hAPP-C105 Tg mice
Lim, H. J., Shim, S. B., Jee, S. W., Lee, S. H., Lim, C. J., Hong, J. T., Sheen, Y. Y., & Hwang, D. Y. (2013) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2012.10.005 · Cited by 77 · see citing works
Signal transduction in Alzheimer disease: p21‐activated kinase signaling requires C‐terminal cleavage of APP at Asp664
Nguyen, T. V., Galván, V., Huang, W., Banwait, S., Tang, H., Zhang, J., & Bredesen, D. E. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05031.x · Cited by 76 · see citing works
Loss of Interleukin Receptor-Associated Kinase 4 Signaling Suppresses Amyloid Pathology and Alters Microglial Phenotype in a Mouse Model of Alzheimer's Disease
Cameron, B., Tse, W., Lamb, R., Li, X., Lamb, B. T., & Landreth, G. E. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1729-12.2012 · Cited by 75 · see citing works
Characterization of the Signaling Pathway Downstream p75 Neurotrophin Receptor Involved in β-Amyloid Peptide-Dependent Cell Death
Costantini, C., Rossi, F., Formaggio, E., Bernardoni, R., Cecconi, D., & Bianca, V. D. (2005) · Journal of Molecular Neuroscience · doi:10.1385/jmn:25:2:141 · Cited by 74 · see citing works
Cdk5 is a major regulator of p38 cascade: relevance to neurotoxicity in Alzheimer’s disease
Chang, K., de Pablo, Y., Lee, H., Lee, H., Smith, M. A., & Shah, K. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06687.x · Cited by 74 · see citing works
Stress and ageing interactions: A paradox in the context of shared etiological and physiopathological processes
Pardon, M. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.02.007 · Cited by 72 · see citing works
A Single c-Jun N-terminal Kinase Isoform (JNK3-p54) Is an Effector in Both Neuronal Differentiation and Cell Death
Waetzig, V., & Herdegen, T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207391200 · Cited by 72 · see citing works
MAPK, β-amyloid and synaptic dysfunction: the role of RAGE
Origlia, N., Arancio, O., Domenici, L., & Yan, S. S. (2009) · Expert Review of Neurotherapeutics · doi:10.1586/ern.09.107 · Cited by 70 · see citing works
Hippocampal metabotropic glutamate receptor long‐term depression in health and disease: focus on mitogen‐activated protein kinase pathways
Sanderson, T. M., Hogg, E. L., Collingridge, G. L., & Corrêa, S. A. L. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13592 · Cited by 70 · see citing works
Genetically Augmenting Aβ42 Levels in Skeletal Muscle Exacerbates Inclusion Body Myositis-Like Pathology and Motor Deficits in Transgenic Mice
Kitazawa, M., Green, K. N., Caccamo, A., & LaFerla, F. M. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.051232 · Cited by 70 · see citing works
Insulin-degrading enzyme: Roles and pathways in ameliorating cognitive impairment associated with Alzheimer's disease and diabetes
Tian, Y., Jing, G., & Zhang, M. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101999 · Cited by 69 · see citing works
Aberrant expressions of pathogenic phenotype in Alzheimer's diseased transgenic mice carrying NSE-controlled APPsw
Hwang, D. Y., Cho, J. S., Lee, S. H., Chae, K. R., Lim, H. J., Min, S. H., Seo, S. J., Song, Y. S., Song, C. W., Paik, S. G., et al. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2003.09.021 · Cited by 69 · see citing works
Early effects of Aβ 1-42 oligomers injection in mice: Involvement of PI3K/Akt/GSK3 and MAPK/ERK1/2 pathways
Morroni, F., Sita, G., Tarozzi, A., Rimondini, R., & Hrelia, P. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.08.002 · Cited by 65 · see citing works
Tau Phosphorylation, Molecular Chaperones, and Ubiquitin E3 Ligase: Clinical Relevance in Alzheimer's Disease
Kumar, P., Jha, N. K., Jha, S. K., Ramani, K., & Ambasta, R. K. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-140933 · Cited by 67 · see citing works
Reactivation of HSV‐1 in the brain of patients with familial Alzheimer's disease
Mori, I., Kimura, Y., Naiki, H., Matsubara, R., Takeuchi, T., Yokochi, T., & Nishiyama, Y. (2004) · Journal of Medical Virology · doi:10.1002/jmv.20133 · Cited by 67 · 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
JNK Activation in Alzheimer’s Disease Is Driven by Amyloid β and Is Associated with Tau Pathology
Solas, M., Vela, S., Smerdou, C., Martišová, E., Martínez-Valbuena, I., Luquín, M. R., & Ramírez, M. J. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00093 · Cited by 42 · see citing works
Modulation of the JNK and p38 pathways by cdk5 protein kinase in a transgenic mouse model of Alzheimer’s disease
Carola Otth, L., Mendoza‐Naranjo, A., Mujica, L., Zambrano, Á., Concha, I. I., & Maccioni, R. B. (2003) · Neuroreport · doi:10.1097/00001756-200312190-00023 · Cited by 54 · see citing works
The JNK/c-Jun cascade and Alzheimer's disease
Okazawa, H., & Estus, S. (2002) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/153331750201700209 · Cited by 97 · see citing works
Inhibition of c-Jun kinase provides neuroprotection in a model of Alzheimer's disease
Braithwaite, S. P., Schmid, R. S., Dong, H., Sung, M.-L. A., Cho, S., Resnick, L., Monaghan, M. M., Hirst, W. D., Essrich, C., Reinhart, P. H., et al. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.04.015 · Cited by 82 · see citing works

Authors: Savage, M. J., Lin, Y.-G., Ciallella, J. R., Flood, D. G., & Scott, R. W.
ORCID: Scott, Richard W.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2002-05-01
Volume: 22
Issue: 9
Pages: 3376-3385
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.22-09-03376.2002
PMC: PMC6758401
OpenAlex: W1558509021
Cited by: 291
References: 61
Citations by year: 2026: 2 · 2025: 9 · 2024: 6 · 2023: 11 · 2022: 10 · 2021: 8 · 2020: 8 · 2019: 15 · 2018: 8 · 2017: 8 · 2016: 16 · 2015: 9 · 2014: 14 · 2013: 9 · 2012: 6
FWCI: 12.81
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: Alzheimer's disease, c-Jun N-terminal kinase, p38 MAPK, amyloid deposition, MAPK signaling, Tg2576 mice, amyloid precursor protein, MAPKAPK4, c-Jun, tau phosphorylation, synaptophysin, synaptic integrity, neuronal loss, hippocampal CA1
MeSH terms: Aging, Alzheimer Disease, Amyloid, Animals, Cell Count, Cerebral Cortex, Disease Models, Animal, Enzyme Activation, Hippocampus, Humans, Immunohistochemistry, Membrane Proteins, Mice, Transgenic, Neurons, Phosphorylation, Signal Transduction, Neurites, Amyloid beta-Protein Precursor, Synaptophysin, tau Proteins, Gene Targeting, Amino Acid Substitution, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, Mice, Presenilin-1

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

Activation of c-Jun N-Terminal Kinase and p38 in an Alzheimer's Disease Model Is Associated with Amyloid Deposition

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks