Primary fibroblasts cultures reveal TDP-43 abnormalities in amyotrophic lateral sclerosis patients with and without SOD1 mutations

Massimiliano Mirabella, Roberto Piacentini, Marco Luigetti, Paolo Maria Rossini

Risultato della ricerca: Contributo in rivistaArticolo in rivista

26 Citazioni (Scopus)

Abstract

TAR DNA-binding protein 43 (TDP-43) is a major component of the pathologic inclusions observed in the motor neurons of amyotrophic lateral sclerosis (ALS) patients. We examined TDP-43 expression in primary fibroblasts cultures from 22 ALS patients, including cases with SOD1 (n = 4), TARDBP (n = 4), FUS (n = 2), and C9ORF72 (n = 3) mutations and 9 patients without genetic defect. By using a phosphorylation-independent antibody, 15 patients showed notable alterations of TDP-43 level in the nuclear or cytoplasmic compartments. In particular, a marked accumulation of TDP-43 was observed in the cytoplasm of all cases with C9ORF72 and TARDBP mutations, 1 patient with FUS mutation and 3 patients without genetic defect. Patients with SOD1 mutations revealed a significant reduction of TDP-43 in the nuclei without cytoplasmic mislocalization. These changes were associated with the presence of truncated and phosphorylated TDP-43 species. Our results show that fibroblasts recapitulate some of hallmark TDP-43 abnormalities observed in neuronal cells. The reduction of full-length TDP-43 level in mutant SOD1 cells indicates that at least some SOD1 mutations alter TDP-43 metabolism.
Lingua originaleEnglish
pagine (da-a)2005.e5-2005.e5-2005.e13
RivistaNeurobiology of Aging
Volume36
DOI
Stato di pubblicazionePubblicato - 2015

Keywords

  • 3′ UTR
  • Amyotrophic lateral sclerosis
  • Fibroblast culture
  • TARDBP
  • TDP-43

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