Vascular endothelial growth factor counteracts the loss of phospho-Akt preceding motor neurone degeneration in amyotrophic lateral sclerosis

• Published in: Neuropathology and applied neurobiology Vol. 33; no. 5; pp. 499 - 509
• Main Authors: Dewil, M., Lambrechts, D., Sciot, R., Shaw, P. J., Ince, P. G., Robberecht, W., Van Den Bosch, L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2007; Blackwell Science
• Subjects: Adult; Aged; amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - drug therapy; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - pathology; Animals; apoptosis; Biological and medical sciences; Blotting, Western; Diseases of the nervous system; Female; Humans; Immunohistochemistry; Male; Medical sciences; Mice; Mice, Transgenic; Middle Aged; motoneurone; Motor Neurons - metabolism; Motor Neurons - pathology; Nerve Degeneration - drug therapy; neurodegeneration; Neurology; Neuroprotective Agents - administration & dosage; Phosphorylation; protein kinase B; Proto-Oncogene Proteins c-akt - drug effects; Proto-Oncogene Proteins c-akt - metabolism; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Rats; Spinal Cord - metabolism; Spinal Cord - pathology; Superoxide Dismutase - genetics; Superoxide Dismutase-1; Transfection; Vascular diseases and vascular malformations of the nervous system; vascular endothelial growth factor; Vascular Endothelial Growth Factor A - administration & dosage; Nervous system diseases; Akt protein kinase; neurodegeneration; Amyotrophic lateral sclerosis; Motor neuron; Vascular endothelium growth factor; vascular endothelial growth factor; Central nervous system disease; Degenerative disease; Degeneration; Spinal cord disease; Apoptosis; motoneurone; protein kinase B
• ISSN: 0305-1846; 1365-2990
• DOI: 10.1111/j.1365-2990.2007.00850.x

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.