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Fatal familial insomnia: mitochondrial and protein synthesis machinery decline in the mediodorsal thalamus

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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.

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FRAU MENDEZ, Margalida, FERNÁNDEZ-VEGA, Iván, ANSOLEAGA, Belén, BLANCO TECH, Rosa, CARMONA MURILLO, Margarita, RÍO FERNÁNDEZ, José antonio del, ZERR, Inga, LLORENS TORRES, Franc, ZARRANZ, Juan j., FERRER, Isidro (ferrer abizanda). Fatal familial insomnia: mitochondrial and protein synthesis machinery decline in the mediodorsal thalamus. _Brain Pathology_. 2017. Vol. 27, núm. 1, pàgs. 95-106. [consulta: 22 de gener de 2026]. ISSN: 1015-6305. [Disponible a: https://hdl.handle.net/2445/140481]

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