title: The reduction of NADH ubiquinone oxidoreductase 24- and 75-kDa subunits in brains of patients with Down syndrome and Alzheimer's disease.
abstract: NADH: ubiquinone oxidoreductase (complex I), one of the most complicated multi-protein enzyme complexes, is important for energy metabolism because it is the initial enzyme of the mitochondrial respiratory chain. Deficiency of complex I is frequently found in various tissues of patients with neurodegenerative disease. Here we studied the protein levels of complex I 24- and 75-kDa subunits in several brain regions from patients with Down syndrome (DS) and Alzheimer's disease (AD). We determined protein levels of complex I 24-, 75-kDa subunits and mitochondrial marker proteins mitochondrial matrix protein P1 (hsp60) and aconitate hydratase from seven brain regions of patients with DS, AD and controls. Proteins were separated by two-dimensional (2-D) gel electrophoresis and identified by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). Complex I 24-kDa subunit was significantly reduced in occipital cortex and thalamus in patients with DS and temporal and occipital cortices in patients with AD. Complex I 75-kDa subunit was significantly reduced in brain regions from patients with DS (temporal, occipital and caudate nucleus) and AD (parietal cortex). Reductions of two subunits of complex I may lead to the impairment of energy metabolism and result in neuronal cell death (apoptosis), a hallmark of both neurodegenerative disorders.
authors.affiliation: Department of Pediatrics, University of Vienna, Austria.
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: R
authors.initials: R
authors.lastname: Vlkolinsky
authors.forename: N
authors.initials: N
authors.lastname: Cairns
authors.forename: M
authors.initials: M
authors.lastname: Fountoulakis
authors.forename: G
authors.initials: G
authors.lastname: Lubec
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000201:enzymology*; D004314:Down Syndrome / Q000378:metabolism*; D004579:Electron Transport; D042967:Electron Transport Complex I; D004734:Energy Metabolism; D006801:Humans; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D008970:Molecular Weight; D009247:NADH, NADPH Oxidoreductases / Q000032:analysis*; D021122:Protein Subunits
chemical_list: D021122:Protein Subunits; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I