Motor Neuron Survival And Lou Gehrig's Disease

On page 131 (Nature Genetics, Vol. 28, No. 2, 01 June 2001), Peter Carmeliet (of University of Leuven, Belgium) and colleagues implicate the vascular endothelial cell growth factor (VEGF) in adult-onset degeneration of motor neurons in mice. They originally set out to modify the 'control' region upstream of the VEGF gene, so as to repress the increased rate of production of VEGF in response to oxygen deprivation (hypoxia). Surprisingly, the mutant mice developed an age-dependent degeneration of motor neurons, reminiscent of ALS in humans. This indicates that a primary cause of ALS may be a chronic deficit in VEGF-dependent supply of blood (and its bio-available oxygen) to motor neurons. The authors also demonstrate that VEGF directly affects the survival of motor neurons, and thus indicate another potential means by which aberrations in VEGF may give rise to ALS.

Pate Skene (of Duke University, USA) and Don Cleveland (of University of California in San Diego, USA) suggest, in an accompanying News & Views article that, of all the neurons in the body, motor neurons are the most sensitive to deficits in the blood supply because they are among the largest cells in the body and thus have extremely high metabolic needs.

The mice obtained by Carmeliet and collaborators provide an interesting animal model with which to explore possible interactions between SOD1, VEGF, and other cellular components in the pathogenesis of motor neuron disorders. Whether mutations affecting VEGF levels result in ALS will now be the focus of intense investigation. And, as VEGF and its receptors are the targets of current anti-cancer drugs-designed to deprive tumors of a blood supply-the possible side effects of such drugs on motor function should draw the attention of oncologists.

CONTACT:

Dr. Peter Carmeliet
University of Leuven
Leuven, Belgium
Telephone: +32 16-34-57-74
Fax: +32 16-34-59-90
Email: peter.carmeliet@med.kuleuven.ac.be

Dr. Pate Skene
Duke University
Durham, North Carolina, USA
Telephone: +1 (919) 681-6346
Email: skene@neuro.duke.edu

Dr. Don W. Cleveland
Ludwig Institute for Cancer Research
La Jolla, California, USA
Telephone: +1 (858) 534-7811
Fax: +1 (619) 534 7659
Email: dcleveland@ucsd.edu

(C) Nature Genetics press release.

Message posted by: Trevor M. D'Souza