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

• 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
• ISSN: 0166-2236; 1878-108X
• DOI: 10.1016/S0166-2236(99)01533-7

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.