Neuroprotective effects of gangliosides may involve inhibition of nitric oxide synthase.
Gangliosides are polar, sugar-containing lipids that are major constituents of neuronal membranes. Gangliosides are neuroprotective in animal models of neurotoxicity and may also be useful in patients with clinical conditions such as spinal cord injury. We show that a series of gangliosides inhibit nitric oxide synthase activity by binding calmodulin. The prevention of glutamate neurotoxicity in cortical cultures by gangliosides closely parallels their potencies in binding calmodulin and inhibiting nitric oxide synthase. Neuroprotective effects of gangliosides may arise from blockade of nitric oxide formation.
Dawson
T M
TM
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Hung
K
K
Dawson
V L
VL
Steiner
J P
JP
Snyder
S H
SH
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002147:Calmodulin / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000037:antagonists & inhibitors*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005732:Gangliosides / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D019001:Nitric Oxide Synthase; D051381:Rats
D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D005732:Gangliosides; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases