Tumour necrosis factor-alpha- vs. growth factor deprivation-promoted cell death: different receptor requirements for mediating nerve growth factor-promoted rescue.

Todd C. Pappas, Francesco Decorti, Nancy J. Macdonald, Kenneth E. Neet, Giulio Taglialatela

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Physiological and pathological aging of the central nervous system (CNS) is characterized by functional neuronal impairments which may lead to perturbed cell homeostasis and eventually to neuronal death. Many toxic events may underlie age-related neurodegeneration. These include the effects of beta amyloid, Tau and mutated presenilin proteins, free radicals and oxidative stress, pro-inflammatory cytokines and lack of growth factor support, which can be individually or collectively involved. Taken individually, these toxicants can induce very diverse cell responses, thus requiring individually targeted corrective interventions upstream of common cell death (apoptotic) pathways. Recent preliminary evidence suggests that the pro-inflammatory cytokine tumour necrosis factor alpha (TNFalpha) and growth factor withdrawal can both activate a common apoptotic pathway in nerve growth factor (NGF)-responsive PC12 cells involving caspase 3, albeit through very distinct upstream pathways: the former through active signalling and the latter through passive or lack of survival signalling. Here, we show that NGF can rescue PC12 cells from both growth factor withdrawal- and TNFalpha-promoted cell death. However, NGF rescue from growth factor withdrawal requires NGF signalling through the high-affinity tyrosine kinase receptor (TrkA), while NGF rescue from TNFalpha-promoted cell death requires NGF signalling through the low-affinity p75NTR receptor. These results strengthen the idea that prevention of age- or pathology-associated neurodegeneration may require varied molecular approaches reflecting the diversity of the toxicants involved, possibly acting simultaneously.

Original languageEnglish (US)
Pages (from-to)83-92
Number of pages10
JournalAging Cell
Volume2
Issue number2
StatePublished - Apr 2003

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Death Domain Receptors
Nerve Growth Factor
Intercellular Signaling Peptides and Proteins
Cell Death
Tumor Necrosis Factor-alpha
PC12 Cells
Presenilins
Cytokines
Poisons
Receptor Protein-Tyrosine Kinases
Amyloid
Caspase 3
Free Radicals
Oxidative Stress
Homeostasis
Central Nervous System
Pathology
Proteins

ASJC Scopus subject areas

  • Cell Biology

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Tumour necrosis factor-alpha- vs. growth factor deprivation-promoted cell death : different receptor requirements for mediating nerve growth factor-promoted rescue. / Pappas, Todd C.; Decorti, Francesco; Macdonald, Nancy J.; Neet, Kenneth E.; Taglialatela, Giulio.

In: Aging Cell, Vol. 2, No. 2, 04.2003, p. 83-92.

Research output: Contribution to journalArticle

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