Connection of lipid peroxide oxidation with the sphingomyelin pathway in the development of Alzheimer's disease.
Alzheimer's disease (AD) is characterized by progressive decline in cognition, memory and intellect. It has been hypothesized that amyloid-beta peptide (A-beta) may have a prominent role in neurodegeneration. Oxidative mechanisms have been implicated in this pathway. There is substantial evidence that inflammatory mechanisms, induced by tumour necrosis factor alpha (TNF-alpha), are also involved in AD. TNF-alpha activates receptors linked to multiple effector systems, including a sphingomyelin pathway and peroxide oxidation. We have determined the changes of neutral sphingomyelinase activity, sphingomyelin and ceramide contents, and the level of lipid peroxide products (conjugated dienes), in the cerebral cortex, hippocampus and cerebellum of rats within 3 h and 7 days of intracerebral injection of A-beta and TNF-alpha. A single injection of A-beta and TNF-alpha has been shown to increase the level of peroxide products in the hippocampus and cerebral cortex within 3 h and 7 days. Sphingomyelinase activity and ceramide levels have been found to increase 7 days after A-beta administration. We found that activation of the sphingomyelin pathway lies downstream from the oxidative stress.
Alessenko
A V
AV
Institute of Biochemical Physics, 4 Kosygin str., Moscow 119991, Russia. ales@sky.chph.ras.ru
Bugrova
A E
AE
Dudnik
L B
LB
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism*
D008054:Lipid Peroxides; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase