Recombinant human TNF-binding protein-1 (rhTBP-1) treatment delays both symptoms progression and motor neuron loss in the wobbler mouse

Paolo Bigini, Mariaelena Repici, Giuseppina Cantarella, Elena Fumagalli, Sara Barbera, Alfredo Cagnotto, Ada De Luigi, Rossella Tonelli, Renato Bernardini, Tiziana Borsello, Tiziana Mennini

Research output: Contribution to journalArticle

Abstract

TNF-α overexpression may contribute to motor neuron death in amyotrophic lateral sclerosis (ALS). We investigated the intracellular pathway associated with TNF-α in the wobbler mouse, a murine model of ALS, at the onset of symptoms. TNF-α and TNFR1 overexpression and JNK/p38MAPK phosphorylation occurred in neurons and microglia in early symptomatic mice, suggesting that this activation may contribute to motor neuron damage. The involvement of TNF-α was further confirmed by the protective effect of treatment with rhTNF-α binding protein (rhTBP-1) from 4 to 9 weeks of age. rhTBP-1 reduced the progression of symptoms, motor neuron loss, gliosis and JNK/p38MAPK phosphorylation in wobbler mice, but did not reduce TNF-α and TNFR1 levels. rhTBP-1 might possibly bind TNF-α and reduce the downstream phosphorylation of two main effectors of the neuroinflammatory response, p38MAPK and JNK.

Original languageEnglish
Pages (from-to)465-476
Number of pages12
JournalNeurobiology of Disease
Volume29
Issue number3
DOIs
Publication statusPublished - Mar 2008

Keywords

  • Amyotrophic lateral sclerosis
  • Glial activation
  • JNK
  • Motor neuron degeneration
  • p38MAPK
  • rhTBP-1
  • TNF-α
  • TNFR1
  • Wobbler

ASJC Scopus subject areas

  • Neurology

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