Oct-1 recruitment to the nuclear envelope in adult-onset autosomal dominant leukodystrophy

Marta Columbaro, Elisabetta Mattioli, Nadir M. Maraldi, Michela Ortolani, Laura Gasparini, Maria Rosaria D'Apice, Diana Postorivo, Anna Maria Nardone, Sofia Avnet, Pietro Cortelli, Rocco Liguori, Giovanna Lattanzi

Research output: Contribution to journalArticlepeer-review


Adult-onset autosomal dominant leukodystrophy (ADLD) is a slowly progressive neurological disorder characterised by pyramidal, cerebellar, and autonomic disturbances. Duplication of the LMNB1 gene is the genetic cause of ADLD, yet the pathogenetic mechanism is not defined. In this study, we analysed cells and muscle tissue from three patients affected by ADLD, carrying an extra copy of the LMNB1 gene. Lamin B1 levels were dramatically increased in ADLD nuclei, both in skin fibroblasts and skeletal muscle fibres. Since lamin B1 is known to bind Oct-1, a transcription factor involved in the oxidative stress pathway, we investigated Oct-1 fate in ADLD. Oct-1 recruitment to the nuclear periphery was increased in ADLD cells, while nucleoplasmic localisation of the transcription factor under oxidative stress conditions was reduced. Importantly, lamin B1 degradation occurring in some, but not all ADLD cell lines, slowed down lamin B1 and Oct-1 accumulation. In skeletal muscle, focal disorganisation of sarcomeres was observed, while IIB-myosin heavy chain, an Oct-1 target gene, was under-expressed and rod-containing fibres were formed. These data show that a high degree of regulation of lamin B1 expression is implicated in the different clinical phenotypes observed in ADLD and show that altered Oct-1 nuclear localisation contributes to the disease phenotype.

Original languageEnglish
Pages (from-to)411-420
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number3
Publication statusPublished - Mar 2013


  • Autosomal dominant leukodystrophy (ADLD)
  • IIB-myosin heavy chain
  • Lamin B1
  • Oct-1
  • Protein degradation

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine


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