Fatal familial insomnia: mitochondrial and protein synthesis machinery decline in the mediodorsal thalamus
| Autor: | Margalida A. Frau-Méndez, Belén Ansoleaga, Franc Llorens, Isidro Ferrer, José Antonio del Río, Inga Zerr, Juan J. Zarranz, Rosa Blanco Tech, Iván Fernández-Vega, Margarita Carmona Tech |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Fatal familial insomnia General Neuroscience Protein subunit SOD2 Mitochondrion Biology medicine.disease Ribosome Pathology and Forensic Medicine Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Mitochondrial respiratory chain Biochemistry Coenzyme Q – cytochrome c reductase medicine Neurology (clinical) Nucleolin 030217 neurology & neurosurgery |
| Zdroj: | Brain Pathology. 27:95-106 |
| ISSN: | 1015-6305 |
| DOI: | 10.1111/bpa.12408 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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