Thalidomide-induced Teratogenesis: History and Mechanisms

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Abstract

Nearly 60 years ago thalidomide was prescribed to treat morning sickness in pregnant women. What followed was the biggest man-made medical disaster ever where over 10000 children were born with a range of severe and debilitating malformations. Despite this, the drug is now used successfully to treat a range of
adult conditions including multiple myeloma and complications of leprosy. Tragically a new generation of thalidomide damaged children has been identified in Brazil. Yet, how thalidomide caused its devastating effects upon the forming embryo remains unclear. However, over the past few years huge strides in our understanding of the molecular mechanisms the drug uses has been elucidated. This review will look at the history of the drug, the range and type of damage the drug caused and outline the mechanisms of action the drug uses including recent molecular advances and new findings. Some of the remaining challenges facing thalidomide biologists are also discussed.
Original languageEnglish
Pages (from-to)140-156
Number of pages17
JournalBirth Defects Research. Part C, Embryo Today: Reviews
Volume105
Issue number2
Early online date4 Jun 2015
DOIs
Publication statusPublished - Jun 2015

Keywords

  • angiogenesis
  • reactive oxygen species
  • cell death
  • cereblon
  • actin cytoskeleton
  • limb development
  • Fgf8
  • Shh
  • phocomelia
  • vascular transition

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