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Int. J. Mol. Sci. 2015, 16(1), 1385-1394; doi:10.3390/ijms16011385

Profiling of Ubiquitination Pathway Genes in Peripheral Cells from Patients with Frontotemporal Dementia due to C9ORF72 and GRN Mutations

Neurology Unit, Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milan 20122, Italy
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Author to whom correspondence should be addressed.
Academic Editor: Kurt A. Jellinger
Received: 21 November 2014 / Accepted: 24 December 2014 / Published: 8 January 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

We analysed the expression levels of 84 key genes involved in the regulated degradation of cellular protein by the ubiquitin-proteasome system in peripheral cells from patients with frontotemporal dementia (FTD) due to C9ORF72 and GRN mutations, as compared with sporadic FTD and age-matched controls. A SABiosciences PCR array was used to investigate the transcription profile in a discovery population consisting of six patients each in C9ORF72, GRN, sporadic FTD and age-matched control groups. A generalized down-regulation of gene expression compared with controls was observed in C9ORF72 expansion carriers and sporadic FTD patients. In particular, in both groups, four genes, UBE2I, UBE2Q1, UBE2E1 and UBE2N, were down-regulated at a statistically significant (p < 0.05) level. All of them encode for members of the E2 ubiquitin-conjugating enzyme family. In GRN mutation carriers, no statistically significant deregulation of ubiquitination pathway genes was observed, except for the UBE2Z gene, which displays E2 ubiquitin conjugating enzyme activity, and was found to be statistically significant up-regulated (p = 0.006). These preliminary results suggest that the proteasomal degradation pathway plays a role in the pathogenesis of FTD associated with TDP-43 pathology, although different proteins are altered in carriers of GRN mutations as compared with carriers of the C9ORF72 expansion. View Full-Text
Keywords: frontotemporal lobar degeneration; progranulin; C9ORF72; ubiquitination; E2 ubiquitin conjugating enzyme frontotemporal lobar degeneration; progranulin; C9ORF72; ubiquitination; E2 ubiquitin conjugating enzyme
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Serpente, M.; Fenoglio, C.; Cioffi, S.M.G.; Bonsi, R.; Arighi, A.; Fumagalli, G.G.; Ghezzi, L.; Scarpini, E.; Galimberti, D. Profiling of Ubiquitination Pathway Genes in Peripheral Cells from Patients with Frontotemporal Dementia due to C9ORF72 and GRN Mutations. Int. J. Mol. Sci. 2015, 16, 1385-1394.

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