Therapeutic benefit of polyamine-modified catalase as a scavenger of hydrogen peroxide and nitric oxide in familial amyotrophic lateral sclerosis transgenics.
Continuous subcutaneous administration of polyamine-modified catalase that has increased permeability at the blood-brain barrier showed both a highly significant delay in onset and an increase in survival in a transgenic mouse model of familial amyotrophic lateral sclerosis having a point mutation in the gene encoding copper/zinc superoxide dismutase. These results suggest that hydrogen peroxide-mediated oxidative stress with subsequent free radical damage involving nitric oxide and possibly hydroxyl radicals in motor neurons may be the culprit in familial amyotrophic lateral sclerosis.
Poduslo
J F
JF
Department of Neurology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Whelan
S L
SL
Curran
G L
GL
Wengenack
T M
TM
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D001812:Blood-Brain Barrier; D002374:Catalase / Q000378:metabolism / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000378:metabolism*; D011700:Putrescine / Q000031:analogs & derivatives / Q000494:pharmacology*; D016019:Survival Analysis
D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D002374:Catalase; D011700:Putrescine