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The reduction of NADH ubiquinone oxidoreductase 24- and 75-kDa
subunits in brains of patients with Down syndrome and Alzheimer’s
disease.
Kim SH, Vlkolinsky R, Cairns N, Fountoulakis M, Lubec G.Department of Pediatrics, University of Vienna, Austria.
NADH: ubiquinone oxidoreductase (complex I), one of the most complicated multiprotein 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 twodimensional
(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.