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Title: Vascular endothelial growth factor counteracts the loss of phospho-Akt preceding motor neurone degeneration in amyotrophic lateral sclerosis
Authors: Dewil, M ×
Lambrechts, Diether
Sciot, Raphael
Shaw, P J
Ince, P G
Robberecht, Wim
Van Den Bosch, Ludo #
Issue Date: Oct-2007
Publisher: Blackwell Scientific Publications
Series Title: Neuropathology and Applied Neurobiology vol:33 issue:5 pages:499-509
Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that results in the selective loss of motor neurones. In the present study, the involvement of the antiapoptotic protein, Akt (protein kinase B), was studied. We found that motor neurones of both sporadic and familial ALS patients lack phospho-Akt, and that motor neurones of mutant SOD1 mice lose activated Akt early in the disease, before the onset of clinical symptoms. In vitro, overexpression of constitutively active Akt protects against mutant SOD1-dependent cell death. In vivo, levels of phospho-Akt in the spinal cord increase after intracerebroventricular administration of vascular endothelial growth factor to mutant SOD1 rats, a treatment we previously described to significantly protect motor neurones. From these results, we conclude that the loss of phospho-Akt could be involved in motor neurone death in ALS, and that therapies upregulating phospho-Akt thus might be of clinical relevance.
URI: 
ISSN: 0305-1846
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Neurology
Vesalius Research Centre (-)
Translational Cell & Tissue Research
Laboratory for Neurobiology (Vesalius Research Center)
Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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