Anti-apoptotic treatment reduces transthyretin deposition in a transgenic mouse model of Familial Amyloidotic Polyneuropathy

Biochim Biophys Acta. 2008 Sep;1782(9):517-22. doi: 10.1016/j.bbadis.2008.05.005. Epub 2008 Jun 3.


Tauroursodeoxycholic acid (TUDCA) is a unique natural compound that acts as a potent anti-apoptotic and anti-oxidant agent, reducing cytotoxicity in several neurodegenerative diseases. Since oxidative stress, apoptosis and inflammation are associated with transthyretin (TTR) deposition in Familial Amyloidotic Polyneuropathy (FAP), we investigated the possible TUDCA therapeutical application in this disease. We show by semi-quantitative immunohistochemistry and western blotting that administration of TUDCA to a transgenic mouse model of FAP decreased apoptotic and oxidative biomarkers usually associated with TTR deposition, namely the ER stress markers BiP and eIF2alpha, the Fas death receptor and oxidation products such as 3-nitrotyrosine. Most important, TUDCA treatment significantly reduced TTR toxic aggregates in as much as 75%. Since TUDCA has no effect on TTR aggregation "in vitro", this finding points for the "in vivo" modulation of TTR aggregation by cellular responses, such as by oxidative stress, ER stress and apoptosis and prompts for the use of this safe drug in prophylactic and therapeutic measures in FAP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Neuropathies, Familial / metabolism*
  • Animals
  • Apoptosis / drug effects*
  • Disease Models, Animal
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / pathology
  • Endoplasmic Reticulum Chaperone BiP
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / metabolism
  • Heat-Shock Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Methionine / genetics
  • Mice
  • Mice, Transgenic
  • Molecular Chaperones / metabolism
  • Mutant Proteins / metabolism
  • Mutation / genetics
  • Oxidation-Reduction / drug effects
  • Prealbumin / chemistry
  • Prealbumin / metabolism*
  • Prealbumin / ultrastructure
  • Protein Structure, Quaternary
  • Taurochenodeoxycholic Acid / pharmacology*
  • Thermodynamics
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism
  • fas Receptor / metabolism


  • Endoplasmic Reticulum Chaperone BiP
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Mutant Proteins
  • Prealbumin
  • fas Receptor
  • 3-nitrotyrosine
  • Tyrosine
  • Taurochenodeoxycholic Acid
  • ursodoxicoltaurine
  • Methionine