Manifold decrease of sialic acid synthase in fetal Down syndrome brain.
BACKGROUND
Down syndrome (DS, trisomy 21) is the most common genetic cause of mental retardation. A large series of biochemical defects have been observed in fetal and adult DS brain that help in unraveling the molecular mechanisms underlying mental retardation.


OBJECTIVE
As sialylation of glycoconjugates plays an important role in brain development, this study aimed to look at the sialic acid metabolism by measuring sialic acid synthase (SAS; N-acetylneuraminate synthase) in early second trimester fetal control and DS brain.


RESULTS
In this regard, protein profiling was performed by two-dimensional gel electrophoresis coupled to matrix-assisted laser desorption/ionization mass-spectrometry followed by database search and subsequent quantification of spot using specific software. SAS, the enzyme catalyzing synthesis of N-acetyl-neuraminic acid (syn: sialic acid) was represented as a single spot and found to be significantly and manifold reduced (P < 0.01) in cortex of fetuses with DS (control vs. DS, 0.052 +/- 0.025 vs. 0.012 +/- 0.006).


CONCLUSIONS
The intriguing finding of the manifold decrease of SAS in DS fetal cerebral cortex as early as in the second trimester of pregnancy may help to explain the brain deficit observed in DS. Decreased SAS may well lead to altered sialic acid metabolism, required for brain development and, more specifically, for sialylation of key brain proteins, including neuronal cell adhesion molecule and myelin associated glycoprotein.
Gulesserian
T
T
Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
Engidawork
E
E
Fountoulakis
M
M
Lubec
G
G
D037881:Aborted Fetus / Q000201:enzymology* / Q000473:pathology; D002540:Cerebral Cortex / Q000201:enzymology* / Q000473:pathology; D004314:Down Syndrome / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006001:Glycoconjugates / Q000378:metabolism; D006801:Humans; D008297:Male; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D009474:Neurons / Q000201:enzymology; D007652:Oxo-Acid-Lyases / Q000378:metabolism*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism
D006001:Glycoconjugates; D018992:Myelin-Associated Glycoprotein; D012794:Sialic Acids; C018730:N-acetylneuraminate synthase; D007652:Oxo-Acid-Lyases