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Journal of Neurology

, Volume 260, Issue 11, pp 2917–2927 | Cite as

Amyotrophic lateral sclerosis: an update on recent genetic insights

  • Yohei Iguchi
  • Masahisa Katsuno
  • Kensuke Ikenaka
  • Shinsuke Ishigaki
  • Gen SobueEmail author
Medical Progress in the Journal of Neurology

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting both upper and lower motor neurons. The prognosis for ALS is extremely poor, but there is a limited course of treatment with only one approved medication. A most striking recent discovery is that TDP-43 is identified as a key molecule that is associated with both sporadic and familial forms of ALS. TDP-43 is not only a pathological hallmark, but also a genetic cause for ALS. Subsequently, a number of ALS-causative genes have been found. Above all, the RNA-binding protein, such as FUS, TAF15, EWSR1 and hnRNPA1, have structural and functional similarities to TDP-43, and physiological functions of some molecules, including VCP, UBQLN2, OPTN, FIG4 and SQSTM1, are involved in a protein degradation system. These discoveries provide valuable insight into the pathogenesis of ALS, and open doors for developing an effective disease-modifying therapy.

Keywords

Amyotrophic lateral sclerosis Motor neuron disease Protein aggregation RNA metabolism 

Notes

Acknowledgments

This work was supported by Grant-in-Aids (KAKENHI) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Nos. 22110005, 21229011 and 23390230) and Core Research for Evolutional Science and Technology (CREST) from the Japan Science and Technology Agency (JST). Figure 3 was reproduced from Iguchi et al. Ref. [36].

Conflicts of interest

None.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Yohei Iguchi
    • 1
    • 2
  • Masahisa Katsuno
    • 1
  • Kensuke Ikenaka
    • 1
  • Shinsuke Ishigaki
    • 1
  • Gen Sobue
    • 1
    Email author
  1. 1.Department of NeurologyNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.The Centre de Recherche de l’Institut Universitaire en Santé Mentale de Québec-CRIUSMQLaval UniversityQuebecCanada

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