ArticleProceedings of the National Academy of Sciences of the United States of America1999
A new mechanism of neurodegeneration: a proinflammatory cytokine inhibits receptor signaling by a survival peptide.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 186 citations in OpenAlex.
- Anti-TNF antibody treatment improves glucocorticoid induced insulin-like growth factor 1 (IGF1) resistance without influencing myoglobin and IGF1 binding proteins 1 and 3.Annals of the rheumatic diseases · 2006Trial
- The Role of Insulin-like Growth Factor I in Mechanisms of Resilience and Vulnerability to Sporadic Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Review
- Anti-Inflammatory Therapies for Treatment of Inflammation-Related Preterm Brain Injury.International journal of molecular sciences · 2021Review
- CNS inflammation and neurodegeneration.The Journal of clinical investigation · 2017Article
- Circulating TNF-α levels increased and correlated negatively with IGF-I in postoperative cognitive dysfunction.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2017Article
- Insulin-Like Growth Factor-1 and Neuroinflammation.Frontiers in aging neuroscience · 2017Review
- IGF-1 mediated phosphorylation of specific IRS-1 serines in Ames dwarf fibroblasts is associated with longevity.Oncotarget · 2015Article
- Neuropathogenesis of Japanese encephalitis in a primate model.PLoS neglected tropical diseases · 2014Article
- Involvement of IRS-1 interaction with ADAM10 in the regulation of neurite extension.Journal of cellular physiology · 2014Article
- Pigment epithelium-derived factor (PEDF) peptide eye drops reduce inflammation, cell death and vascular leakage in diabetic retinopathy in Ins2(Akita) mice.Molecular medicine (Cambridge, Mass.) · 2012Article
- Diabetic retinopathy: Role of inflammation and potential therapies for anti-inflammation.World journal of diabetes · 2010Article
- IGF-IR in neuroprotection and brain tumors.Frontiers in bioscience (Landmark edition) · 2009Review
- Interleukin-1 beta impairs brain derived neurotrophic factor-induced signal transduction.Neurobiology of aging · 2008Article
- Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence.The journals of gerontology. Series A, Biological sciences and medical sciences · 2008Review
- Neuronal death by oxidative stress involves activation of FOXO3 through a two-arm pathway that activates stress kinases and attenuates insulin-like growth factor I signaling.Molecular biology of the cell · 2008Article
- Neuronal apoptosis and inflammatory responses in the central nervous system of a rabbit treated with Shiga toxin-2.Journal of neuroinflammation · 2008Article
- Interleukin-1beta interferes with signal transduction induced by neurotrophin-3 in cortical neurons.Brain research · 2008Article
- Interaction between serine phosphorylated IRS-1 and beta1-integrin affects the stability of neuronal processes.Journal of neuroscience research · 2007Article
- Effects of insulin-like growth factor-I on cytokine-induced sickness behavior in mice.Brain, behavior, and immunity · 2006Article
Corrections and comments
- Retraction · 2009-07-28Duplication of/in Image · Investigation by Company/Institution · Investigation by ORI · Manipulation of Images · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author · · There is a Findings of scientific misconduct for this article (HD Venters): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259696/;
- Commented on by
- Retracted
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Heightened expression of both a proinflammatory cytokine, tumor necrosis factor alpha (TNF-alpha), and a survival peptide, insulin-like growth factor I (IGF-I), occurs in diverse diseases of the central nervous system, including Alzheimer's disease, multiple sclerosis, the AIDS-dementia complex, and cerebral ischemia. Conventional roles for these two proteins are neuroprotection by IGF-I and neurotoxicity by TNF-alpha. Although the mechanisms of action for IGF-I and TNF-alpha in the central nervous system originally were established as disparate and unrelated, we hypothesized that the signaling pathways of these two cytokines may interact during neurodegeneration. Here we show that concentrations of TNF-alpha as low as 10 pg/ml markedly reduce the capacity of IGF-I to promote survival of primary murine cerebellar granule neurons. TNF-alpha suppresses IGF-I-induced tyrosine phosphorylation of insulin receptor substrate 2 (IRS-2) and inhibits IRS-2-precipitable phosphatidylinositol 3'-kinase activity. These experiments indicate that TNF-alpha promotes IGF-I receptor resistance in neurons and inhibits the ability of the IGF-I receptor to tyrosine-phosphorylate the IRS-2 docking molecule and to subsequently activate the critical downstream enzyme phosphatidylinositol 3'-kinase. This intracellular crosstalk between discrete cytokine receptors reveals a novel pathway that leads to neuronal degeneration whereby a proinflammatory cytokine inhibits receptor signaling by a survival peptide.
Indexed as
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.