A new concept in neurodegeneration: TNFα is a silencer of survival signals

The p55 receptor for the pro-inflammatory cytokine tumor necrosis factor α (TNFα) is best characterized by its ability to induce signals that trigger cell death. However, this is not the only way in which this TNF receptor kills neurons. A new view of neurodegeneration has recently emerged in which...

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Bibliographic Details
Published in:Trends in Neurosciences 2000-04, Vol.23 (4), p.175-180
Main Authors: Venters, Homer D., Dantzer, Robert, Kelley, Keith W.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
General aspects. Models. Methods
IGF1
Life Sciences
Neurodegeneration
P13 kinase
SOSS
TNF
Vertebrates: nervous system and sense organs
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Summary:The p55 receptor for the pro-inflammatory cytokine tumor necrosis factor α (TNFα) is best characterized by its ability to induce signals that trigger cell death. However, this is not the only way in which this TNF receptor kills neurons. A new view of neurodegeneration has recently emerged in which a TNF receptor induces death through the ‘silencing of survival signals’ (SOSS), such as phosphatidylinositol 3′ kinase (PI3 kinase), that are activated by the insulin-like growth factor 1 receptor. This mechanism of intracellular crosstalk is the most pathophysiologically relevant action of TNFα in the brain and is applicable to a broad number of receptors that are localized on the same cell. Treatment of the more-devastating and costly neurodegenerative diseases of our time might be best promoted by increasing the efficacy of neuronal survival factors using new approaches aimed at inhibiting the SOSS.
ISSN:0166-2236
1878-108X
DOI:10.1016/S0166-2236(99)01533-7