Early glycoxidation damage in brains from Down's syndrome.
In Down's syndrome, the presence of three copies of chromosome 21 is associated with premature aging and progressive mental retardation sharing the pathological features of Alzheimer disease. Early cortical dysgenesis and late neuronal degeneration are probably caused by an overproduction of amyloid beta-peptide, followed by an increased cellular oxidation. Interestingly, chromosome 21 codes for superoxide-dismutase and amyloid beta precursor resulting, in Down's syndrome, in an overflow of these gene products and metabolites. We studied Down's fetal brain cortex to evaluate the presence and amount of lipid and protein oxidation markers; moreover, we quantified two forms of glycation end products that are known to be involved in the process of cellular oxidation. All these parameters are significantly increased in Down's fetal brains in comparison to controls, providing the evidence that accelerated brain glycoxidation occurs very early in the life of Down's syndrome subjects.
Odetti
P
P
Department of Internal Medicine (DIMI), University of Genova, Italy.
Angelini
G
G
Dapino
D
D
Zaccheo
D
D
Garibaldi
S
S
Dagna-Bricarelli
F
F
Piombo
G
G
Perry
G
G
Smith
M
M
Traverso
N
N
Tabaton
M
M
D000447:Aldehydes / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism; D004314:Down Syndrome / Q000378:metabolism*; D005865:Gestational Age; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D006801:Humans; D015227:Lipid Peroxidation; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D009646:Norleucine / Q000031:analogs & derivatives / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011758:Pyrroles / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000447:Aldehydes; D016564:Amyloid beta-Protein Precursor; D017127:Glycation End Products, Advanced; D011758:Pyrroles; D017392:Thiobarbituric Acid Reactive Substances; C059571:2-formyl-5-(hydroxymethyl)pyrrole-1-norleucine; D009646:Norleucine; D001120:Arginine; C062187:pentosidine; D013482:Superoxide Dismutase; C027576:4-hydroxy-2-nonenal; D008239:Lysine