Publications

by Keyword: Protein synthesis


By year:[ 2017 | 2016 | 2015 | 2014 | 2013 | 2012 | 2011 | 2010 | 2009 | 2008 | 2007 | 2006 | 2005 ]

Frau-Méndez, Margalida A., Fernández-Vega, Iván, Ansoleaga, Belén, Blanco, Rosa, Carmona, Margarita, Antonio del Rio, Jose, Zerr, Inga, Llorens, Franc, Zarranz, Juan José, Ferrer, Isidro, (2017). Fatal familial insomnia: Mitochondrial and protein synthesis machinery decline in the mediodorsal thalamus Brain Pathology 27, (1), 95-106

The expression of subunits of mitochondrial respiratory complexes and components of the protein synthesis machinery from the nucleolus to the ribosome was analyzed in the mediodorsal thalamus in seven cases of Fatal Familial Insomnia (FFI) compared with age-matched controls. NDUFB8 (complex I subunit), SDHB (complex II subunit), UQCRC2 (complex III subunit), COX2 (complex IV subunit) and ATP50 (complex V subunit) expression levels, as revealed by western blotting, were reduced in FFI. Voltage-dependent anion channel (VDAC) and ATP5H were also reduced due to the marked depopulation of neurons. In contrast, a marked increase in superoxide dismutase 2 (SOD2) was found in reactive astrocytes thus suggesting that astrocytes are key factors in oxidative stress responses. The histone-binding chaperones nucleolin and nucleoplasmin 3, and histone H3 di-methylated K9 were markedly reduced together with a decrease in the expression of protein transcription elongation factor eEF1A. These findings show severe impairment in the expression of crucial components of mitochondrial function and protein synthesis in parallel with neuron loss in mediodorsal thalamus at terminal stages of FFI. Therapeutic measures must be taken long before the appearance of clinical symptoms to prevent the devastating effects of FFI.

Keywords: Fatal familial insomnia, Mitochondria, Protein synthesis, Mitochondrial respiratory chain, Nucleolus, Ribosome


Ansoleaga, B., Garcia-Esparcia, Paula, Llorens, Franc, Hernández-Ortega, Karina, Carmona Tech, Margarita, Antonio del Rio, José, Zerr, Inga, Ferrer, Isidro, (2016). Altered mitochondria, protein synthesis machinery, and purine metabolism are molecular contributors to the pathogenesis of Creutzfeldt–Jakob disease Journal of Neuropathology & Experimental Neurology 75, (8), 755-769

Neuron loss, synaptic decline, and spongiform change are the hallmarks of sporadic Creutzfeldt–Jakob disease (sCJD), and may be related to deficiencies in mitochondria, energy metabolism, and protein synthesis. To investigate these relationships, we determined the expression levels of genes encoding subunits of the 5 protein complexes of the electron transport chain, proteins involved in energy metabolism, nucleolar and ribosomal proteins, and enzymes of purine metabolism in frontal cortex samples from 15 cases of sCJD MM1 and age-matched controls. We also assessed the protein expression levels of subunits of the respiratory chain, initiation and elongation translation factors of protein synthesis, and localization of selected mitochondrial components. We identified marked, generalized alterations of mRNA and protein expression of most subunits of all 5 mitochondrial respiratory chain complexes in sCJD cases. Expression of molecules involved in protein synthesis and purine metabolism were also altered in sCJD. These findings point to altered mRNA and protein expression of components of mitochondria, protein synthesis machinery, and purine metabolism as components of the pathogenesis of CJD.

Keywords: Creutzfeldt–Jakob disease, Electron transport chain, Mitochondria, Oxidative phosphorylation, Protein synthesis, Purine.


Comments are closed