Profiling of ubiquitination pathway genes in peripheral cells from patients with frontotemporal dementia due to C9oRF72 and GRN mutations

Maria Serpente, Chiara Fenoglio, Sara M G Cioffi, Rossana Bonsi, Andrea Arighi, Giorgio G. Fumagalli, Laura Ghezzi, Elio Scarpini, Daniela Galimberti

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1385-1394
Number of pages10
JournalInternational Journal of Molecular Sciences
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 8 2015

Keywords

  • C9ORF72
  • E2 ubiquitin Conjugating enzyme
  • Frontotemporal lobar degeneration
  • Progranulin
  • Ubiquitination

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications

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