Decreased protein levels of complex I 30-kDa subunit in fetal Down syndrome brains

Defects of mitochondrial electron transport enzymes have been implicated in the pathogenesis of several neurodegenerative diseases. In previous work, we reported decreased protein levels of mitochondrial electron transport en zyme subunits in adult brain with Down syndrome (DS). However it is not cle ar whether cellular damage due to mitochondrial defects in brain of DS fetu s begins in utero. Here we investigated the protein levels of mitochondrial electron transport enzymes in fetal DS brain using the proteomic technolog ies. Two-dimensional (2-D) gel electrophoresis, matrix-assisted laser desor ption ionization mass spectroscopy (MALDI-MS) and specific software for qua ntification were used. The protein levels of complex I 30-kDa subunit were significantly decreased in cerebral cortex of fetal DS brain. We conclude t hat decreased mitochondrial electron transport enzyme subunits in fetal DS brains could contribute to the impaired energy and free radical metabolism affecting brain development in DS fetus. Furthermore, the defects of mitoch ondrial electron enzymes shown in adult DS brains could begin in utero and continue during the life span of the individual with DS.