Curcumin could reduce the monomer of TTR with Tyr114Cys mutation via autophagy in cell model of familial amyloid polyneuropathy

Drug Des Devel Ther. 2014 Oct 31:8:2121-8. doi: 10.2147/DDDT.S70866. eCollection 2014.

Abstract

Transthyretin (TTR) familial amyloid polyneuropathy (FAP) is an autosomal dominant inherited neurodegenerative disorder caused by various mutations in the transthyretin gene. We aimed to identify the mechanisms underlying TTR FAP with Tyr114Cys (Y114C) mutation. Our study showed that TTR Y114C mutation led to an increase in monomeric TTR and impaired autophagy. Treatment with curcumin resulted in a significant decrease of monomeric TTR by recovering autophagy. Our research suggests that impairment of autophagy might be involved in the pathogenesis of TTR FAP with Y114C mutation, and curcumin might be a potential therapeutic approach for TTR FAP.

Keywords: autophagy; curcumin; familial amyloid polyneuropathy; transthyretin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Neuropathies, Familial / drug therapy*
  • Amyloid Neuropathies, Familial / genetics
  • Amyloid Neuropathies, Familial / pathology*
  • Autophagy / drug effects*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Curcumin / pharmacology*
  • Cysteine / genetics*
  • HEK293 Cells
  • Humans
  • Mutation / genetics
  • Prealbumin / chemistry
  • Prealbumin / genetics*
  • Prealbumin / metabolism*
  • Tyrosine / genetics*

Substances

  • Prealbumin
  • Tyrosine
  • Curcumin
  • Cysteine