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

International Journal of Molecular Sciences

Maria Serpente¹  Chiara Fenoglio²  Sara M. G. Cioffi²  Rossana Bonsi²  Andrea Arighi²  Giorgio G. Fumagalli²  Laura Ghezzi²  Elio Scarpini²  Daniela Galimberti² 

[1] Neurology Unit, Department of Pathophysiology and Transplantation, “Dino Ferrari” Center, University of Milan, Fondazione Ca’ Granda, IRCCS Ospedale Maggiore Policlinico, Milan 20122, Italy;

关键词: frontotemporal lobar degeneration;    progranulin;    C9ORF72;    ubiquitination;    E2 ubiquitin conjugating enzyme;   

DOI  :  10.3390/ijms16011385

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.