Reduction of nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal Down Syndrome brain

Information on the various factors leading to impairments in the developing brain of fetal Down Syndrome patients is limited to few histological repor ts. We therefore attempted to describe expression levels of proteins in bra in using the proteomic technique of two-dimensional electrophoresis with su bsequent mass spectroscopical identification of protein spots and quantific ation with specific software. Cortical tissue was obtained from autopsy of human fetal abortus. Protein levels of GTP-binding nuclear protein ran, gua nine nucleotide-binding protein g(o), alpha subunit 2, guanine nucleotide-b inding protein g(i)/g(s)/g(t) beta subunit 1, -beta subunit 2, guanine nucl eotide-binding protein beta subunit 5, nucleoside diphosphate kinase A, nuc leoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta, Rho GDP- dissociation inhibitor 1, biphosphate 3'-nucleotidase, small glutamine-rich tetra-tricopeptide repeat-containing protein and histidine triad nucleotid e-binding protein were studied. Quantification revealed statistically significant reduced levels of nucleos ide diphosphate kinase B, Rab GDP-dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal DS brain as compared to controls . We conclude that in early prenatal life proteins involved in neural differe ntiation, migration and synaptic transmission are impaired in DS cortex. Th ese results may help to understand the abundant mechanisms leading to abnor malities in the wiring, structure and function of DS brain.