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

6533b7d8fe1ef96bd1269b34

RESEARCH PRODUCT

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

D. Pennacchini Pietro Veglianese M. Bao Cutrona B. Pozzi Caterina Bendotti D. Lo Coco D. Lo Coco J.p. Julien G. Gowing Massimo Tortarolo R. Magnoni

subject

p38 mitogen-activated protein kinases MAP Kinase Kinase 3 Mice Transgenic MAP Kinase Kinase 6 Biology MAP Kinase Kinase Kinase 5 p38 Mitogen-Activated Protein Kinases Receptors Tumor Necrosis Factor Cellular and Molecular Neuroscience Mice Superoxide Dismutase-1 Downregulation and upregulation Animals Humans ASK1 RNA Messenger fas Receptor Phosphorylation Receptor Protein kinase A Molecular Biology P38MAPK cascade Motor Neurons Kinase Superoxide Dismutase Tumor Necrosis Factor-alpha Amyotrophic Lateral Sclerosis JNK Mitogen-Activated Protein Kinases Receptors Interleukin-1 Cell Biology Cell biology Enzyme Activation Mice Inbred C57BL Disease Models Animal Tumor Necrosis Factor Decoy Receptors Spinal Cord Receptors Tumor Necrosis Factor Type I Disease Progression Tumor necrosis factor alpha Signal Transduction

description

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 TNFalpha receptors (TNFR1 and TNFR2), but not IL1beta 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.

year	journal	country	edition	language
2005-06-16	Molecular and cellular neurosciences

10.1016/j.mcn.2005.09.009 https://pubmed.ncbi.nlm.nih.gov/16219474