中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (2): 173-180.doi: 10.4103/1673-5374.226377

• 综述:退行性病与再生 •    下一篇

DNA可塑性与肌萎缩性侧索硬化症

  

  • 收稿日期:2018-01-16 出版日期:2018-02-15 发布日期:2018-02-15

DNA plasticity and damage in amyotrophic lateral sclerosis

Diane Penndorf, Otto W. Witte, Alexandra Kretz   

  1. Hans Berger Department of Neurology, University Hospital Jena, Jena, Thuringia, Germany
  • Received:2018-01-16 Online:2018-02-15 Published:2018-02-15
  • Contact: Alexandra Kretz, M.D.,alexandra.kretz@med.uni-jena.de.
  • Supported by:

    The study was supported by the Ministry for Economics, Sciences and Digital Society of Thuringia (TMWWDG), in the framework of the ProExcellence Initiative RegenerAging (RegenerAging-FSU-I-03/14 to AK), and by the Interdisciplinary Center for Clinical Research (IZKF) Jena (Project FF01 to AK).

摘要:

orcid:0000-0001-5880-603X(Alexandra Kretz)

Abstract:

The pathophysiology of amyotrophic lateral sclerosis (ALS) is particularly challenging due to the heterogeneity of its clinical presentation and the diversity of cellular, molecular and genetic peculiarities involved. Molecular insights unveiled several novel genetic factors to be inherent in both familial and sporadic disease entities, whose characterizations in terms of phenotype prediction, pathophysiological impact and putative prognostic value are a topic of current researches. However, apart from genetically well-defined high-confidence and other susceptibility loci, the role of DNA damage and repair strategies of the genome as a whole, either elicited as a direct consequence of the underlying genetic mutation or seen as an autonomous parameter, in the initiation and progression of ALS, and the different cues involved in either process are still incompletely understood. This mini review summarizes current knowledge on DNA alterations and counteracting DNA repair strategies in ALS pathology and discusses the putative role of unconventional DNA entities including transposable elements and extrachromosomal circular DNA in the disease process. Focus is set on SOD1-related pathophysiology, with extension to FUS, TDP-43 and C9ORF72 mutations. Advancing our knowledge in the field will contribute to an improved understanding of this relentless disease, for which therapeutic options others than symptomatic approaches are almost unavailable.

Key words: amyotrophic lateral sclerosis, DNA damage and repair, extrachromosomal circular DNA, microDNA, nuclear pore complex, SOD1 mutations, TDP-43 pathology, transposable elements