Transcription-dependent and -independent control of neuronal survival by the PI3K–Akt signaling pathway

Brunet, Anne; Datta, Sandeep Robert; Greenberg, Michael E.

doi:10.1016/s0959-4388(00)00211-7

Cited by 1,060 publications

(792 citation statements)

References 84 publications

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“…[10]), including the inhibition of the function of FOXO transcription factors that upregulate key death genes, the activation of T-cell factor (TCF) via inactivation of GSK-3β, the activation of NF-kappa B, inactivation of p53, and the prevention of the release of cytochrome c from the mitochondria via Bag1-dependent phosphorylation of BAD [19]. One or more of these pathways may participate in the effect of IL-1β in compromising the Akt-mediated BDNF survival signal and it will be interesting to elucidate their relative contribution in future studies.…”

Section: Discussionmentioning

confidence: 99%

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

Tong

Balázs

Soi-ampornkul³

et al. 2008

Neurobiology of Aging

185

142

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The expression of IL-1 is elevated in the CNS in diverse neurodegenerative disorders, including Alzheimer's disease. The hypothesis was tested that IL-1β renders neurons vulnerable to degeneration by interfering with BDNF-induced neuroprotection. In trophic support-deprived neurons, IL-1β 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 PLCγ, was decreased. Activation of CREB, a target of these signaling pathways, was severely depressed by IL-1β. As the cytokine did not influence TrkB receptor and PLCγ activation, IL-1β might have interfered with BDNF signaling at the docking step conveying activation to the PI3-K/Akt and Ras/MAPK pathways. Indeed, IL-1β 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-1β places neurons at risk by interfering with BDNF signaling involving a ceramide-associated mechanism. Keywords IL-1β; BDNF; signal transduction; cortical neuronsInterleukin-1 (IL-1) is a pluripotent proinflammatory cytokine that is a potent activator of host defense responses to infection and injury both in the periphery and the CNS [59]. However, IL-1 can also exacerbate damage in the CNS resulting from acute insults, such as © 2007 Elsevier Inc. All rights reserved. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript cerebral ischemia and trauma, and circumstantial evidence is consistent with a similar role in chronic neurological diseases, such as multiple sclerosis, Parkinson's disease and Alzheimer's disease (AD) [48]. Furthermore, recent genetic studies highlighted the relevance of IL-1 in AD pathogenesis, showing that specific polymorphisms in the IL-1 gene cluster are associated with greatly increased risk for AD, especially for the earlier onset of the disease [23,50]. The view that inflammatory processes play an important role in pathogenesis has been supported by epidemiological studies, showing that certain antiinflammatory drugs result in a slower progression of the disease [2,8,43,77] and in transgenic AD models decrease the number of dystrophic neurites, activated microglia and IL-1 expression [35], although such drugs also modulate the production of the a...

show abstract

Section: Discussionmentioning

confidence: 99%

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

Tong

Balázs

Soi-ampornkul³

et al. 2008

Neurobiology of Aging

185

142

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“…However, for genes of the subclasses O and P, similarities in their expression patterns are less obvious. Finally, it will be interesting to determine whether Drosophila FoxO (fd88A) is a component of the Akt pathway during insulin signaling and the regulation of apoptosis, as are its vertebrate and C. elegans orthologs (Ogg et al, 1997;Brunet et al, 2001a).…”

Section: Discussionmentioning

confidence: 99%

Survey of forkhead domain encoding genes in the Drosophila genome: Classification and embryonic expression patterns

Lee

Frasch

2004

Developmental Dynamics

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Genetic approaches in Drosophila led to the identification of Forkhead, the prototype of forkhead domain transcription factors that are now known to comprise an evolutionarily conserved family of proteins with essential roles in development and differentiation. Sequence analysis of the recently published genomic scaffold sequence from Drosophila melanogaster has allowed us to determine the presumably full complement of forkhead domain encoding genes in this species. We show herein that the Drosophila genome contains 17 forkhead domain encoding genes; 13 of these genes have orthologs in chordate species, and their products can be assigned to 10 of the 17 forkhead domain subclasses known from chordates. One Drosophila forkhead domain gene only has a Caenorhabditis elegans ortholog and may represent a subclass that is absent in chordates, while the remaining three cannot be classified. We present the mRNA expression patterns of seven previously uncharacterized members of this gene family and show that they are expressed in tissues from all three germ layers, including central and peripheral nervous system, epidermis, salivary gland primordia, endoderm, somatic mesoderm, and hemocyte progenitors. Furthermore, the expression patterns of two of these genes, fd19B and fd102C, suggest a role for them as gap genes during early embryonic head segmentation.

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“…Akt is a serine-threonine kinase whose activation via phosphorylation can control the balance between survival and death signaling in brain [32]. Several laboratories have shown that nonanesthetic, neuroprotective forms of brain preconditioning enhance Akt activation after cerebral ischemia in male and neonatal animals [31,[33][34][35][36].…”

Section: Akt Activationmentioning

confidence: 99%

Inhalational anesthetics as preconditioning agents in ischemic brain

Wang

Traystman

Murphy

2008

Current Opinion in Pharmacology

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Transcription-dependent and -independent control of neuronal survival by the PI3K–Akt signaling pathway

Cited by 1,060 publications

References 84 publications

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

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

Survey of forkhead domain encoding genes in the Drosophila genome: Classification and embryonic expression patterns

Inhalational anesthetics as preconditioning agents in ischemic brain

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