Upstream regulators and downstream effectors of NF-κB in Alzheimer’s disease

Shi, Zhe-Min; Han, Ya-Wei; Han, Xiao-Hui; Zhang, Kun; Chang, Ya-Nan; Hu, Zhi-Mei; Qi, Hai-Xia; Ting, Chen; Zhen, Zhang; Hong, Wei

doi:10.1016/j.jns.2016.05.022

Cited by 125Alzheimer's disease research and treatmentsNF-κB Signaling PathwaysNeuroinflammation and Neurodegeneration Mechanisms

Upstream regulators and downstream effectors of NF-κB in Alzheimer’s disease

Shi, Zhe-Min, Han, Ya-Wei, Han, Xiao-Hui, Zhang, Kun, Chang, Ya-Nan, Hu, Zhi-Mei, Qi, Hai-Xia, Ting, Chen +2 more·2016·Journal of the Neurological Sciences

DOI 10.1016/j.jns.2016.05.022

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Abstract

Since Alzheimer's disease (AD) is becoming the prevalent dementia in the whole world, more underlying mechanisms are emerging. Long time has the transcription factor NF-κB been identified to participate in AD pathogenesis, various studies have focused on the causes and effects of AD that are linked to NF-κB. In this review we discuss diverse environmental stimuli including oxidative stress, neuroinflammation and metabolism, involved signaling pathways such as PI3K/AKT, MAPK and AGE/RAGE/GSK-3 and newly found ncRNAs that mediate neuron toxicity or neuron protection through NF-κB activation and the following response associated with the same factors in AD. These may provide future orientation of investigation at transcription level and support efficient treatment to AD by a better understanding of the upstream regulators and downstream effectors of NF-κB.

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Neuroinflammation can be attenuated by reducing expression of NF-κB-p65 via NLRP3 pathways.
“Neuroinflammation is one of the major factors of AD and other disorders related to cholinergic transmission. It can be attenuated by reducing the expression of NF-κB-p65 via NLRP3 pathways.”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [141]
Targeting transcription factor NF-κβp65 could be a novel approach for treatment of AD.
“Thus targeting the transcription factor (NF-κβp65) could be the novel approach for the treatment of AD.”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [141]

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IκB Kinase γ/Nuclear Factor-κB-Essential Modulator (IKKγ/NEMO) Facilitates RhoA GTPase Activation, which, in Turn, Activates Rho-associated Kinase (ROCK) to Phosphorylate IKKβ in Response to Transforming Growth Factor (TGF)-β1
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The regulation of the UCH-L1 gene by transcription factor NF-κB in podocytes
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Cyclopamine Modulates γ-Secretase-mediated Cleavage of Amyloid Precursor Protein by Altering Its Subcellular Trafficking and Lysosomal Degradation
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Involvement of Astrocytes in Alzheimer’s Disease from a Neuroinflammatory and Oxidative Stress Perspective
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Astrocytes and Aging
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PI3K Signaling in Neurons: A Central Node for the Control of Multiple Functions
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Microenvironment Remodeling Micelles for Alzheimer's Disease Therapy by Early Modulation of Activated Microglia
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Eriodictyol Attenuates LPS-Induced Neuroinflammation, Amyloidogenesis, and Cognitive Impairments via the Inhibition of NF-κB in Male C57BL/6J Mice and BV2 Microglial Cells
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Astrocytes as a Therapeutic Target in Alzheimer’s Disease–Comprehensive Review and Recent Developments
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Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy
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Molecular Pharmacology of Rosmarinic and Salvianolic Acids: Potential Seeds for Alzheimer’s and Vascular Dementia Drugs
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Toxin-Induced Experimental Models of Learning and Memory Impairment
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A Potential Link Between Visceral Obesity and Risk of Alzheimer’s Disease
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Nutrition and AGE‐ing: Focusing on Alzheimer’s Disease
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Neuroprotective effects of INT-777 against Aβ1–42-induced cognitive impairment, neuroinflammation, apoptosis, and synaptic dysfunction in mice
Wu, X. G., Lv, Y., Du, Y., Chen, F., Reed, M. N., Hu, M. Y., Suppiramaniam, V. D., Tang, S., & Hong, H. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.06.018 · Cited by 100 · see citing works
Intracerebroventricular injection of resveratrol ameliorated Aβ-induced learning and cognitive decline in mice
Yu, Q., Shang, L., Liao, Z., Su, H., Jing, H., Wu, B., Bi, K., & Jia, Y. (2018) · Metabolic Brain Disease · doi:10.1007/s11011-018-0348-6 · Cited by 97 · see citing works
Fucoxanthin, a Marine Carotenoid, Attenuates β ‐Amyloid Oligomer‐Induced Neurotoxicity Possibly via Regulating the PI3K/Akt and the ERK Pathways in SH‐SY5Y Cells
Lin, J., Yu, J., Zhao, J., Zhang, K., Zheng, J., Wang, J., Huang, C., Zhang, J., Yan, X., Gerwick, W. H., et al. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/6792543 · Cited by 92 · see citing works
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Nuclear factor‐kappa B (NF‐κB) in pathophysiology of Parkinson disease: Diverse patterns and mechanisms contributing to neurodegeneration
Dolatshahi, M., Hameghavandi, M. H. R., Sabahi, M., & Rostamkhani, S. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15242 · Cited by 85 · see citing works
The Cross-Talk Between Sphingolipids and Insulin-Like Growth Factor Signaling: Significance for Aging and Neurodegeneration
Jęśko, H. M., Stępień, A., Lukiw, W. J., & Strosznajder, R. P. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1286-3 · Cited by 85 · see citing works
The Neuroprotection of Verbascoside in Alzheimer’s Disease Mediated through Mitigation of Neuroinflammation via Blocking NF-κB-p65 Signaling
Chen, S., Liu, H., Wang, S., Jiang, H., Gao, L., Wang, L., Teng, L., Wang, C., & Wang, D. (2022) · Nutrients · doi:10.3390/nu14071417 · Cited by 79 · see citing works
Nutraceuticals: An emerging therapeutic approach against the pathogenesis of Alzheimer’s disease
Sadhukhan, P., Saha, S., Dutta, S., Mahalanobish, S., & Sil, P. C. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.11.028 · Cited by 66 · see citing works
Inhibition of miR-128 Abates Aβ-Mediated Cytotoxicity by Targeting PPAR-γ via NF-κB Inactivation in Primary Mouse Cortical Neurons and Neuro2a Cells
Geng, L., Zhang, T., Liu, W., & Chen, Y. (2018) · Yonsei Medical Journal · doi:10.3349/ymj.2018.59.9.1096 · Cited by 65 · see citing works
Melatonin ameliorates Aβ42‐induced alteration of β APP ‐processing secretases via the melatonin receptor through the Pin1/ GSK 3β/ NF ‐κB pathway in SH ‐ SY 5Y cells
Chinchalongporn, V., Shukla, M., & Govitrapong, P. (2018) · Journal of Pineal Research · doi:10.1111/jpi.12470 · Cited by 66 · see citing works
Astroglial activation: Current concepts and future directions
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NF-κB-Induced Upregulation of miR-146a-5p Promoted Hippocampal Neuronal Oxidative Stress and Pyroptosis via TIGAR in a Model of Alzheimer’s Disease
Lei, B., Liu, J., Yao, Z., Xiao, Y., Zhang, X., Zhang, Y., & Xu, J. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.653881 · Cited by 59 · see citing works
Autism Spectrum Disorder: Signaling Pathways and Prospective Therapeutic Targets
Baranova, J., Dragunas, G., Botelho, M. C. S., Ayub, A. L. P., Bueno-Alves, R., Alencar, R. R., Papaiz, D. D., Sogayar, M. C., Ulrich, H., & Correa, R. G. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00882-7 · Cited by 59 · see citing works
An emerging role of astrocytes in aging/neuroinflammation and gut-brain axis with consequences on sleep and sleep disorders
Gudkov, S. V., Burmistrov, D. E., Kondakova, E. V., Sarimov, R. M., Yarkov, R. S., Franceschi, C., & Vedunova, M. V. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101775 · Cited by 56 · see citing works
Prenatal exposure to bisphenol A alters the transcriptome-interactome profiles of genes associated with Alzheimer’s disease in the offspring hippocampus
Sukjamnong, S., Thongkorn, S., Kanlayaprasit, S., Saeliw, T., Hussem, K., Warayanon, W., Hu, V. W., Tencomnao, T., & Sarachana, T. (2020) · Scientific Reports · doi:10.1038/s41598-020-65229-0 · Cited by 56 · see citing works
Iridoids and other monoterpenes in the Alzheimer’s brain: Recent development and future prospects
Habtemariam, S. (2018) · Molecules · doi:10.3390/molecules23010117 · Cited by 55 · see citing works
Morin attenuates memory deficits in a rat model of Alzheimer's disease by ameliorating oxidative stress and neuroinflammation
Mohammadi, N., Asle‐Rousta, M., Rahnema, M., & Amini, R. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174506 · Cited by 55 · see citing works
Zerumbone ameliorates behavioral impairments and neuropathology in transgenic APP/PS1 mice by suppressing MAPK signaling
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Isoorientin, a GSK-3β inhibitor, rescues synaptic dysfunction, spatial memory deficits and attenuates pathological progression in APP/PS1 model mice
Tan, X., Liang, Z., Li, Y., Zhi, Y., Yi, L., Bai, S., Forest, K. H., Nichols, R. A., Dong, Y., & Li, Q. X. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112968 · Cited by 52 · see citing works
Protective effect of alpha-linoleic acid on Aβ-induced oxidative stress, neuroinflammation, and memory impairment by alteration of α7 nAChR and NMDAR gene expression in the hippocampus of rats
Tofighi, N., Asle‐Rousta, M., Rahnema, M., & Amini, R. (2021) · NeuroToxicology · doi:10.1016/j.neuro.2021.06.002 · Cited by 50 · see citing works
Parthenolide alleviates microglia‐mediated neuroinflammation via MAPK/TRIM31/NLRP3 signaling to ameliorate cognitive disorder
Fan, M., Wang, C., Zhao, X., Jiang, Y. Z., & Wang, C. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110287 · Cited by 49 · see citing works
NF‐E2‐related factor 2 activation boosts antioxidant defenses and ameliorates inflammatory and amyloid properties in human Presenilin‐1 mutated Alzheimer's disease astrocytes
Oksanen, M., Hyötyläinen, I., Trontti, K., Rõlova, T., Wojciechowski, S., Koskuvi, M., Viitanen, M. H., Levonen, A., Hovatta, I., Roybon, L., et al. (2019) · Glia · doi:10.1002/glia.23741 · Cited by 49 · see citing works
c-Jun N-Terminal Kinase Inhibitors as Potential Leads for New Therapeutics for Alzheimer’s Diseases
Rehfeldt, S. C. H., Majolo, F., Goettert, M. I., & Laufer, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249677 · Cited by 46 · see citing works
Polyphenols Derived from Lychee Seed Suppress Aβ (1-42)-Induced Neuroinflammation
Tang, Y., Xiong, R., Wu, A., Yu, C., Zhao, Y., Qiu, W., Wang, X., Teng, J., Liu, J., Chen, H., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19072109 · Cited by 47 · see citing works
Combination of schisandrin and nootkatone exerts neuroprotective effect in Alzheimer’s disease mice model
Yu, Q., Cheng, X., Jing, H., Yan, T., Xiao, F., Wu, B., Bi, K., & Jia, Y. (2019) · Metabolic Brain Disease · doi:10.1007/s11011-019-00475-4 · Cited by 47 · see citing works
Eriodictyol inhibits high glucose‐induced extracellular matrix accumulation, oxidative stress, and inflammation in human glomerular mesangial cells
Bai, J., Wang, Y., Zhu, X., & Shi, J. (2019) · Phytotherapy Research · doi:10.1002/ptr.6463 · Cited by 46 · see citing works
Long non-coding RNA H19 in atherosclerosis: what role?
Shi, X., Wei, Y., Li, H., Jiang, T., Zheng, X., Yin, K., & Zhao, G.-J. (2020) · Molecular Medicine · doi:10.1186/s10020-020-00196-w · Cited by 46 · see citing works
Isoliquiritigenin Confers Neuroprotection and Alleviates Amyloid-β42-Induced Neuroinflammation in Microglia by Regulating the Nrf2/NF-κB Signaling
Fu, Y., & Jia, J. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.638772 · Cited by 45 · see citing works
Neuroprotective effect of alpha‐pinene is mediated by suppression of the TNF‐α/NF‐κB pathway in Alzheimer's disease rat model
Khan‐Mohammadi‐Khorrami, M., Asle‐Rousta, M., Rahnema, M., & Amini, R. (2022) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.23006 · Cited by 42 · see citing works
Pinoresinol diglucoside attenuates neuroinflammation, apoptosis and oxidative stress in a mice model with Alzheimer’s disease
Lei, S., Wu, S., Wang, G., Li, B., Liu, B., & Xia, L. (2021) · Neuroreport · doi:10.1097/wnr.0000000000001583 · Cited by 41 · see citing works
Tenuifolin Attenuates Amyloid-β42-Induced Neuroinflammation in Microglia Through the NF-κB Signaling Pathway
Chen, S., & Jia, J. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200077 · Cited by 40 · see citing works
Cell death and survival pathways in Alzheimer's disease: an integrative hypothesis testing approach utilizing -omic data sets
Brokaw, D. L., Piras, I. S., Mastroeni, D., Weisenberger, D. J., Nolz, J., Delvaux, E., Serrano, G. E., Beach, T. G., Huentelman, M. J., & Coleman, P. D. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.06.022 · Cited by 38 · see citing works
Zfra restores memory deficits in Alzheimer's disease triple‐transgenic mice by blocking aggregation of TRAPPC6AΔ, SH3GLB2, tau, and amyloid β, and inflammatory NF‐κB activation
Lee, M., Shih, Y., Lin, S., Chang, J., Lin, Y., Sze, C., Kuo, Y., & Chang, N. (2017) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2017.02.001 · Cited by 37 · see citing works
Parthenolide ameliorates 3-nitropropionic acid-induced Huntington’s disease-like aberrations via modulating NLRP3 inflammasome, reducing microglial activation and inducing astrocyte shifting
Noureldeen, M. E., Shahin, N. N., Amin, H. A. A., El‐Sawalhi, M. M., & Ghaiad, H. R. (2024) · Molecular Medicine · doi:10.1186/s10020-024-00917-5 · Cited by 37 · see citing works
Prevention and Treatment Strategies for Alzheimer’s Disease: Focusing on Microglia and Astrocytes in Neuroinflammation
Zhang, S.-S., Gao, Z., Feng, L., & Li, M. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s483412 · Cited by 38 · see citing works
Inhibitory effect of taxifolin on mast cell activation and mast cell-mediated allergic inflammatory response
Pan, S., Zhao, X., Ji, N., Shao, C., Fu, B., Zhang, Z., Wang, R., Qiu, Y., Jin, M., & Kong, D. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.03.038 · Cited by 34 · see citing works
The Cytokine CX3CL1 and ADAMs/MMPs in Concerted Cross-Talk Influencing Neurodegenerative Diseases
Iemmolo, M., Ghersi, G., & Bivona, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098026 · Cited by 33 · see citing works
Transcriptomic analysis of glutamate-induced HT22 neurotoxicity as a model for screening anti-Alzheimer’s drugs
Prasansuklab, A., Sukjamnong, S., Theerasri, A., Hu, V. W., Sarachana, T., & Tencomnao, T. (2023) · Scientific Reports · doi:10.1038/s41598-023-34183-y · Cited by 33 · see citing works
Network Pharmacology‐Based Identification of Potential Targets of Lonicerae japonicae Flos Acting on Anti‐Inflammatory Effects
Guo, X., Xiao, Y., Zheng, B., Zhang, L., Zhang, F., Zhang, Y., Li, J., Pu, G., Zhang, L., & Wu, H. (2021) · BioMed Research International · doi:10.1155/2021/5507003 · Cited by 32 · see citing works
Inhibition of GPR17 with cangrelor improves cognitive impairment and synaptic deficits induced by Aβ1–42 through Nrf2/HO-1 and NF-κB signaling pathway in mice
Jin, S., Wang, X., Xiang, X., Wu, Y., Hu, J., Li, Y., Dong, Y. L., Tan, Y., & Wu, X. G. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108335 · Cited by 32 · see citing works
Classic Prescription, Kai-Xin-San, Ameliorates Alzheimer’s Disease as an Effective Multitarget Treatment: From Neurotransmitter to Protein Signaling Pathway
Guo, S., Wang, J., Xu, H., Rong, W., Gao, C. H., Yuan, Z., Xie, F., Bi, K., Zhang, Z., & Li, Q. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/9096409 · Cited by 30 · see citing works
Retracted
Neuronal Glial Crosstalk: Specific and Shared Mechanisms in Alzheimer’s Disease
Chavda, V. K., Singh, K., Patel, V., Mishra, M., & Mishra, A. K. (2022) · Brain Sciences · doi:10.3390/brainsci12010075 · Cited by 29 · see citing works
Vitegnoside Mitigates Neuronal Injury, Mitochondrial Apoptosis, and Inflammation in an Alzheimer’s Disease Cell Model via the p38 MAPK/JNK Pathway
Wang, Q., Jiang, H., Wang, L., Yi, H., Li, Z., & Liu, R. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190640 · Cited by 28 · see citing works
A Dichotomous Role for FABP7 in Sleep and Alzheimer’s Disease Pathogenesis: A Hypothesis
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Authors: Shi, Z.-M., Han, Y.-W., Han, X.-H., Zhang, K., Chang, Y.-N., Hu, Z.-M., Qi, H.-X., Ting, C., Zhen, Z., & Hong, W.
Affiliations: Tianjin Medical University (CN)
Tianjin Medical University General Hospital (CN)
ORCID: Zhang, Kun
Qi, Hai-Xia
Ting, Chen
Venue: Journal of the Neurological Sciences
Publisher: Elsevier BV
Published: 2016-07
Volume: 366
Pages: 127-134
ISSN: 0022-510X (ISSN-L)
DOI: 10.1016/j.jns.2016.05.022
OpenAlex: W2379046857
Cited by: 125
References: 98
Citations by year: 2026: 9 · 2025: 4 · 2024: 14 · 2023: 14 · 2022: 17 · 2021: 14 · 2020: 13 · 2019: 13 · 2018: 16 · 2017: 9 · 2016: 2
FWCI: 1.57
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of the Neurological Sciences (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: Alzheimer's disease, NF-κB, upstream regulators, downstream effectors, oxidative stress, neuroinflammation, PI3K/Akt signaling, MAPK signaling, non-coding RNA, neurotoxicity, neuroprotection, transcriptional regulation
MeSH terms: Alzheimer Disease, Animals, Humans, NF-kappa B

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Upstream regulators and downstream effectors of NF-κB in Alzheimer’s disease

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