ArticleMolecular biology of the cell2008
Tumor necrosis factor alpha regulates responses to nerve growth factor, promoting neural cell survival but suppressing differentiation of neuroblastoma cells.
Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 30 citations in OpenAlex.
- Intra-cluster receptor density (IRD): A molecular switch for TNFR1 clusters' signaling.Science advances · 2026Article
- Nerve Growth Factor: A Dual Activator of Noradrenergic and Cholinergic Systems of the Rat Ovary.Frontiers in endocrinology · 2021Article
- Marked expression of TNF receptors in human peritendinous tissues including in nerve fascicles with axonal damage - Studies on tendinopathy and tennis elbow.Journal of musculoskeletal & neuronal interactions · 2017Article
- Sustained TNF production by central nervous system infiltrating macrophages promotes progressive autoimmune encephalomyelitis.Journal of neuroinflammation · 2016Article
- TNFα reverse signaling promotes sympathetic axon growth and target innervation.Nature neuroscience · 2013Article
- Integration of apoptosis signal-regulating kinase 1-mediated stress signaling with the Akt/protein kinase B-IκB kinase cascade.Molecular and cellular biology · 2013Article
- The role of dorsal root ganglia activation and brain-derived neurotrophic factor in multiple sclerosis.Journal of cellular and molecular medicine · 2012Article
- TNF-α expression in Schwann cells is induced by LPS and NF-κB-dependent pathways.Neurochemical research · 2012Article
- Characterization and functional analysis of the 5'-flanking promoter region of the mouse Tcf3 gene.Molecular and cellular biochemistry · 2012Article
- Cancer induces cardiomyocyte remodeling and hypoinnervation in the left ventricle of the mouse heart.PloS one · 2011Article
- Vitamin B12 deficiency reduces proliferation and promotes differentiation of neuroblastoma cells and up-regulates PP2A, proNGF, and TACE.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Although nerve growth factor (NGF) promotes survival of neurons, tumor necrosis factor alpha (TNF-alpha) contributes to cell death triggered by NGF depletion, through TNF-alpha receptor (TNFR) 1. In contrast to this effect, TNF-alpha can promote neural cell survival via TNF-alpha receptor TNFR2. Although these findings demonstrate pivotal roles of TNF-alpha and NGF in cell fate decisions, cross-talk between these signaling pathways has not been clarified. We find that NGF can induce TNF-alpha synthesis through the nuclear factor-kappaB transcription factor. This provides a new basis for examining the cross-talk between NGF and TNF-alpha. Inhibition of TNFR2 shows opposite effects on two downstream kinases of NGF, extracellular signal-regulated kinase (Erk) and Akt. It increases Erk activation by NGF, and this increased activation induces differentiation of neuroblastoma cell lines. Reciprocally, inhibition of TNFR2 decreases Akt activation by NGF. Consistent with an essential role of Akt in survival signaling, inhibition of TNF-alpha signaling decreases NGF-dependent survival of neurons from rat dorsal root ganglia. Thus, NGF and NGF-induced TNF-alpha cooperate to activate Akt, promoting survival of normal neural cells. However, the NGF-induced TNF-alpha suppresses Erk activation by NGF, blocking NGF-induced differentiation of neuroblastoma cells. TNFR2 signaling could be a novel target to modulate cell responses to NGF.
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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.