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  • Freischmidt, Axel (author)

Serum microRNAs in patients with genetic amyotrophic lateral sclerosis and pre-manifest mutation carriers

  • Article/chapterEnglish2014

Publisher, publication year, extent ...

  • 2014-09-05
  • Oxford University Press (OUP),2014
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-98911
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-98911URI
  • https://doi.org/10.1093/brain/awu249DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Knowledge about the nature of pathomolecular alterations preceding onset of symptoms in amyotrophic lateral sclerosis is largely lacking. It could not only pave the way for the discovery of valuable therapeutic targets but might also govern future concepts of pre-manifest disease modifying treatments. MicroRNAs are central regulators of transcriptome plasticity and participate in pathogenic cascades and/or mirror cellular adaptation to insults. We obtained comprehensive expression profiles of microRNAs in the serum of patients with familial amyotrophic lateral sclerosis, asymptomatic mutation carriers and healthy control subjects. We observed a strikingly homogenous microRNA profile in patients with familial amyotrophic lateral sclerosis that was largely independent from the underlying disease gene. Moreover, we identified 24 significantly downregulated microRNAs in pre-manifest amyotrophic lateral sclerosis mutation carriers up to two decades or more before the estimated time window of disease onset; 91.7% of the downregulated microRNAs in mutation carriers overlapped with the patients with familial amyotrophic lateral sclerosis. Bioinformatic analysis revealed a consensus sequence motif present in the vast majority of downregulated microRNAs identified in this study. Our data thus suggest specific common denominators regarding molecular pathogenesis of different amyotrophic lateral sclerosis genes. We describe the earliest pathomolecular alterations in amyotrophic lateral sclerosis mutation carriers known to date, which provide a basis for the discovery of novel therapeutic targets and strongly argue for studies evaluating presymptomatic disease-modifying treatment in amyotrophic lateral sclerosis.

Subject headings and genre

  • amyotrophic lateral sclerosis
  • microRNA
  • mutation carriers
  • SOD1
  • C9ORF72

Added entries (persons, corporate bodies, meetings, titles ...)

  • Mueller, Kathrin (author)
  • Zondler, Lisa (author)
  • Weydt, Patrick (author)
  • Volk, Alexander E. (author)
  • Bozic, Anze Losdorfer (author)
  • Walter, Michael (author)
  • Bonin, Michael (author)
  • Mayer, Benjamin (author)
  • von Arnim, Christine A. F. (author)
  • Otto, Markus (author)
  • Dieterich, Christoph (author)
  • Holzmann, Karlheinz (author)
  • Andersen, PeterUmeå universitet,Klinisk neurovetenskap,Department of Neurology, Ulm University, Ulm, Germany;Virtual Helmholtz Institute RNA dysmetabolism in Amyotrophic Lateral Sclerosis and Fronto-temporal Dementia, Germany(Swepub:umu)pean0001 (author)
  • Ludolph, Albert C. (author)
  • Danzer, Karin M. (author)
  • Weishaupt, Jochen H. (author)
  • Umeå universitetKlinisk neurovetenskap (creator_code:org_t)

Related titles

  • In:Brain: Oxford University Press (OUP)137:11, s. 2938-29500006-89501460-2156

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