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Title: Combined transcriptomics and proteomics in frontal cortex area 8 in frontotemporal lobar degeneration linked to C9ORF72 expansion
Author: Andrés Benito, Pol
Gelpi, Ellen
Povedano, Mònica
Ausin, Karina
Fernández Irigoyen, Joaquín
Santamaría, Enrique
Ferrer, Isidro (Ferrer Abizanda)
Keywords: Lòbul frontal
Lòbul temporal
Expressió gènica
Degeneració (Patologia)
Frontal lobe
Temporal lobe
Gene expression
Degeneration (Pathology)
Issue Date: 8-Apr-2019
Publisher: IOS Press
Abstract: Background: frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions (FTLD-TDP) may appear as sporadic (sFTLD-TDP) or linked to mutations in various genes including expansions of the non-coding region of C9ORF72 (c9FTLD). Objective: analysis of differential mRNA and protein expression in the frontal cortex in c9FLTD and evaluation with previous observations in frontal cortex in sFTLD-TDP and amyotrophic lateral sclerosis with TDP-43 inclusions. Methods: microarray hybridization and mass spectrometry-based quantitative proteomics followed by RT-qPCR, gel electrophoresis, and western blotting in frontal cortex area 8 in 19 c9FTLD cases and 14 age- and gender-matched controls. Results: microarray hybridization distinguish altered gene transcription related to DNA recombination, RNA splicing regulation, RNA polymerase transcription, myelin synthesis, calcium regulation, and ubiquitin-proteasome system in c9FTLD; proteomics performed in the same tissue samples pinpoints abnormal protein expression involving apoptosis, inflammation, metabolism of amino acids, metabolism of carbohydrates, metabolism of membrane lipid derivatives, microtubule dynamics, morphology of mitochondria, neuritogenesis, neurotransmission, phagocytosis, receptor-mediated endocytosis, synthesis of reactive oxygen species, and calcium signaling in c9FTLD. Conclusion: transcriptomics and proteomics, as well as bioinformatics processing of derived data, reveal similarly altered pathways in the frontal cortex in c9FTLD, but different RNAs and proteins are identified by these methods. Combined non-targeted '-omics' is a valuable approach to deciphering altered molecular pathways in FTLD provided that observations are approached with caution when assessing human postmortem brain samples.
Note: Versió postprint del document publicat a:
It is part of: Journal of Alzheimer's Disease, 2019, vol. 68, num. 3, p. 1287-1307
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ISSN: 1387-2877
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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