Title: Inhibition of p38 mitogen activated protein kinase activation and mutant SOD1(G93A)-induced motor neuron death
Authors: Dewil, Maarten ×
dela Cruz, Vidal F
Van Den Bosch, Ludo
Robberecht, Wim #
Issue Date: May-2007
Publisher: Blackwell Science
Series Title: Neurobiology of Disease vol:26 issue:2 pages:332-341
Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the selective loss of motor neurons. Stress activated protein kinases (SAPK) have been suggested to play a role in the pathogenesis of ALS. We studied the relevance of p38 MAPK for motor neuron degeneration in the mutant SOD1 mouse. Increased levels of phospho-p38 MAPK were present in the motor neurons and microglia of the ventral spinal cord. The p38 MAPK-inhibitor, SB203580, completely inhibited mutant SOD1-induced apoptosis of motor neurons and blocked LPS-induced activation of microglia. Semapimod, a p38 MAPK inhibitor suitable for clinical use, prolonged survival of mutant SOD1 mice to a limited extent, but largely protected motor neurons and proximal axons from mutant SOD1-induced degeneration. Our data confirm the abnormal activation of p38 MAPK in mutant SOD1 mice and the involvement of p38 MAPK in mutant SOD1-induced motor neuron death. We demonstrate the effect of p38 MAPK inhibition on survival of mutant SOD1 mice and reveal a dissociation between the effect on survival of motor neurons and that on survival of the animal, the latter likely depending on the integrity of the entire motor axon.
ISSN: 0969-9961
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Neurology
Laboratory for Neurobiology (VIB-KU Leuven Center for Brain & Disease Research)
× corresponding author
# (joint) last author

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