Reduced aldehyde dehydrogenase levels in the brain of patients with Down syndrome.
Aldehyde dehydrogenase (ALDH) is a key enzyme in fructose, acetaldehyde and oxalate metabolism and represents a major detoxification system for reactive carbonyls and aldehydes. In the brain, ALDH exerts a major function in the metabolism of biogenic aldehydes, norepinephrine, dopamine and diamines and gamma-aminobutyric acid. Subtractive hybridization studies in Down Syndrome (DS) fetal brain showed that mRNA for ALDH are downregulated. Here we studied the protein levels in the brain of adult patients. The proteins from five brain regions of 9 aged patients with DS and 9 controls were analyzed by two-dimensional (2-D) gel electrophoresis and identified by matrix-assisted laser desorption ionization mass spectrometry. ALDH levels were reduced in the brain regions of at least half of the patients with Down Syndrome, as compared to controls. The decreased ALDH levels in the DS brain may result in accumulation of aldehydes which can lead to the formation of plaques and tangles reflecting abnormally cross-linked, insoluble and modified proteins, found in aged DS brain. Furthermore, we constructed a 2-Dmap including approximately 120 identified human brain proteins.
Lubec
G
G
Department of Pediatrics, University of Vienna, Austria.
Labudova
O
O
Cairns
N
N
Berndt
P
P
Langen
H
H
Fountoulakis
M
M
D000328:Adult; D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000201:enzymology* / Q000254:growth & development; D004314:Down Syndrome / Q000201:enzymology* / Q000235:genetics; D005333:Fetus; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000444:Aldehyde Dehydrogenase