Interleukin-1beta impairs brain derived neurotrophic factor-induced signal transduction.

Interleukin-1beta impairs brain derived neurotrophic factor-induced signal transduction. Research Abstract Details 

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Interleukin-1beta impairs brain derived neurotrophic factor-induced signal transduction. Abstract Text:

The expression of IL-1 is elevated in the CNS in diverse neurodegenerative disorders, including Alzheimer's disease. The hypothesis was tested that IL-1beta renders neurons vulnerable to degeneration by interfering with BDNF-induced neuroprotection. In trophic support-deprived neurons, IL-1beta 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 PLCgamma, was decreased. Activation of CREB, a target of these signaling pathways, was severely depressed by IL-1beta. As the cytokine did not influence TrkB receptor and PLCgamma activation, IL-1beta might have interfered with BDNF signaling at the docking step conveying activation to the PI3-K/Akt and Ras/MAPK pathways. Indeed, IL-1beta 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-1beta places neurons at risk by interfering with BDNF signaling involving a ceramide-associated mechanism.

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Interleukin-1beta impairs brain derived neurotrophic factor-induced signal transduction. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Neurobiology of aging

VOLUME: 29

Page Numbers: 1380-93

Journal Abbreviation: Neurobiol. Aging

ISSN: 1558-1497

DAY: 27

MONTH: 04

YEAR: 2007

Interleukin-1beta impairs brain derived neurotrophic factor-induced signal transduction. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Interleukin-1beta impairs brain derived neurotrophic factor-induced signal transduction.

AFFILIATION: University of California Irvine, Institute for Brain Aging and Dementia, Irvine, California, CA 92697-4540, United States.

Country: United States

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MEDLINETA: Neurobiol Aging

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