Activation of the p38MAPK cascade is associated with upregulation of TNF alpha receptors in the spinal motor neurons of mouse models of familial ALS

P. Veglianese, D. Lo Coco, M. Bao Cutrona, R. Magnoni, D. Pennacchini, B. Pozzi, G. Gowing, J. P. Julien, M. Tortarolo, C. Bendotti

Research output: Contribution to journalArticle

Abstract

Phosphorylated p38 mitogen-activated protein kinase (p38MAPK), but not activated c-jun-N-terminal kinase (JNK), increases in the motor neurons of transgenic mice overexpressing ALS-linked SOD1 mutants at different stages of the disease. This effect is associated with a selective increase of phosphorylated MKK3-6, MKK4 and ASK1 and a concomitant upregulation of the TNFα receptors (TNFR1 and TNFR2), but not IL1β and Fas receptors. Activation of both p38 MAPK and JNK occurs in the activated microglial cells of SOD1 mutant mice at the advanced stage of the disease; however, this effect is not accompanied by the concomitant activation of the upstream kinases ASK1 and MKK3,4,6, while both the TNFRs are overexpressed in these cells. No changes of the upstream p38MAPK cascade kinases or TNFRs occur in reactive astrocytes. These findings highlight the activation of a selective intracellular signaling pathway in the motor neurons of SOD1 mutant mice, which is likely implicated in their death.

Original languageEnglish
Pages (from-to)218-231
Number of pages14
JournalMolecular and Cellular Neuroscience
Volume31
Issue number2
DOIs
Publication statusPublished - Feb 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

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