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.

Profiling of ubiquitination pathway genes in peripheral cells from patients with frontotemporal dementia due to C9ORF72 and GRN mutations / M. Serpente, C. Fenoglio, S.M.G. Cioffi, R. Bonsi, A. Arighi, G.G. Fumagalli, L. Ghezzi, E. Scarpini, D. Galimberti. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 16:1(2015), pp. 1385-1394. [10.3390/ijms16011385]

Profiling of ubiquitination pathway genes in peripheral cells from patients with frontotemporal dementia due to C9ORF72 and GRN mutations

M. Serpente
Primo
;
C. Fenoglio
Secondo
;
R. Bonsi;A. Arighi;G.G. Fumagalli;L. Ghezzi;E. Scarpini
Penultimo
;
D. Galimberti
Ultimo
2015

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.
Aged; DNA-Binding Proteins; Down-Regulation; Female; Frontotemporal Dementia; Genotype; Humans; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Polymorphism, Single Nucleotide; Proteins; Ubiquitin-Conjugating Enzymes; Ubiquitination
Settore MED/26 - Neurologia
2015
Article (author)
File in questo prodotto:
File Dimensione Formato  
6. Serpente et al. ijms.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 782.05 kB
Formato Adobe PDF
782.05 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/423281
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 13
social impact