Vascular endothelial growth factor overexpression delays neurodegeneration and prolongs survival in amyotrophic lateral sclerosis mice.
We sought genetic evidence for the involvement of neuronal vascular endothelial growth factor (VEGF) in amyotrophic lateral sclerosis (ALS). Mice expressing human ALS mutant superoxide dismutase-1 (SOD1) were crossed with mice that overexpress VEGF in neurons (VEGF+/+). We report that SOD1(G93A)/VEGF+/+ double-transgenic mice show delayed motor neuron loss, delayed motor impairment, and prolonged survival compared with SOD1(G93A) single transgenics. These findings indicate that neuronal VEGF protects against motor neuron degeneration, and may have therapeutic implications for ALS.
Wang
Yaoming
Y
Buck Institute for Age Research, Novato, California 94945, USA.
Mao
Xiao Ou
XO
Xie
Lin
L
Banwait
Surita
S
Marti
Hugo H
HH
Greenberg
David A
DA
Jin
Kunlin
K
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology; D009410:Nerve Degeneration / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D000072105:Superoxide Dismutase-1; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology
C000606290:SOD1 protein, human; D042461:Vascular Endothelial Growth Factor A; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1