Cited by 223Nerve injury and regenerationNeuroinflammation and Neurodegeneration MechanismsCytokine Signaling Pathways and Interactions

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Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction

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Tong, Liqi, Balazs, Robert, Soiampornkul, Rungtip, Thangnipon, Wipawan, Cotman, Carl W.·2008·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2007.02.027PMC PMC4052889

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Abstract

The expression of IL-1 is elevated in the CNS in diverse neurodegenerative disorders, including Alzheimer's disease. The hypothesis was tested that IL-1 beta renders neurons vulnerable to degeneration by interfering with BDNF-induced neuroprotection. In trophic support-deprived neurons, IL-1 beta compromised the PI3-K/Akt pathway-mediated protection by BDNF and suppressed Akt activation. The effect was specific as in addition to Akt, the activation of MAPK/ERK, but not PLC gamma, was decreased. Activation of CREB, a target of these signaling pathways, was severely depressed by IL-1 beta. As the cytokine did not influence TrkB receptor and PLC gamma activation, IL-1 beta might have interfered with BDNF signaling at the docking step conveying activation to the PI3-K/Akt and Ras/MAPK pathways. Indeed, IL-1 beta suppressed the activation of the respective scaffolding proteins IRS-1 and Shc; this effect might involve ceramide generation. IL-1-induced interference with BDNF neuroprotection and signal transduction was corrected, in part, by ceramide production inhibitors and mimicked by the cell-permeable C2-ceramide. These results suggest that IL-1 beta places neurons at risk by interfering with BDNF signaling involving a ceramide-associated mechanism.

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Authors: Tong, L., Balazs, R., Soiampornkul, R., Thangnipon, W., & Cotman, C. W.
Affiliations: University of California, Irvine (US)
Mahidol University (TH)
Corresponding author: Tong, Liqi
ORCID: Tong, Liqi
Thangnipon, Wipawan
Cotman, Carl W.
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 2008-09
Volume: 29
Issue: 9
Pages: 1380-1393
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/j.neurobiolaging.2007.02.027
PMC: PMC4052889
OpenAlex: W2015851283
Cited by: 222
References: 88
Citations by year: 2026: 9 · 2025: 10 · 2024: 18 · 2023: 12 · 2022: 13 · 2021: 12 · 2020: 16 · 2019: 8 · 2018: 14 · 2017: 18 · 2016: 13 · 2015: 8 · 2014: 11 · 2013: 18 · 2012: 15
FWCI: 2.79
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (P01AG000538)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Keywords: IL-1β, brain-derived neurotrophic factor, neuroprotection, PI3K/Akt signaling, ERK signaling, CREB activation, TrkB receptor, IRS-1, Shc, ceramide, neurodegeneration, Alzheimer's disease, neuroinflammation, signal transduction
MeSH terms: Animals, Cells, Cultured, Cerebral Cortex, Neurons, Signal Transduction, Apoptosis, Brain-Derived Neurotrophic Factor, Rats, Interleukin-1beta

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Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction

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