Cellular and Molecular Life Sciences

, Volume 68, Issue 9, pp 1569–1579

Teratogenic effects of thalidomide: molecular mechanisms

Authors

  • Takumi Ito
    • Solutions Research LaboratoryTokyo Institute of Technology
  • Hideki Ando
    • Graduate School of Bioscience and BiotechnologyTokyo Institute of Technology
    • Solutions Research LaboratoryTokyo Institute of Technology
    • Graduate School of Bioscience and BiotechnologyTokyo Institute of Technology
Review

DOI: 10.1007/s00018-010-0619-9

Cite this article as:
Ito, T., Ando, H. & Handa, H. Cell. Mol. Life Sci. (2011) 68: 1569. doi:10.1007/s00018-010-0619-9

Abstract

Fifty years ago, prescription of the sedative thalidomide caused a worldwide epidemic of multiple birth defects. The drug is now used in the treatment of leprosy and multiple myeloma. However, its use is limited due to its potent teratogenic activity. The mechanism by which thalidomide causes limb malformations and other developmental defects is a long-standing question. Multiple hypotheses exist to explain the molecular mechanism of thalidomide action. Among them, theories involving oxidative stress and anti-angiogenesis have been widely supported. Nevertheless, until recently, the direct target of thalidomide remained elusive. We identified a thalidomide-binding protein, cereblon (CRBN), as a primary target for thalidomide teratogenicity. Our data suggest that thalidomide initiates its teratogenic effects by binding to CRBN and inhibiting its ubiquitin ligase activity. In this review, we summarize the biology of thalidomide, focusing on the molecular mechanisms of its teratogenic effects. In addition, we discuss the questions still to be addressed.

Keywords

ThalidomideTeratogenicityOxidative stressAnti-angiogenesisCereblonFibroblast growth factor 8

Copyright information

© Springer Basel AG 2010