The role of fibrinogen glycation in ATTR: Evidence for chaperone activity loss in disease

Daniel Fonseca, Samuel Gilberto, Cristina Ribeiro-Silva, Raquel Ribeiro, Ines Batista Guinote, Susana Saraiva, Ricardo Jorge Gomes, Elia Mateus, Ana S. Viana, Eduardo Barroso, Ana Ponces Freire, Patrick Freire, Carlos Cordeiro, Goncalo Da Costa

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Transthyretin amyloidosis (ATTR) belongs to a class of disorders caused by protein misfolding and aggregation. ATTR is a disabling disorder of autosomal dominant trait, where transthyretin (TTR) forms amyloid deposits in different organs, causing dysfunction of the peripheral nervous system. We previously discovered that amyloid fibrils from ATTR patients are glycated by methylglyoxal. Even though no consensus has been reached about the actual role of methylglyoxal-derived advanced glycation end-products in amyloid diseases, evidence collected so far points to a role for protein glycation in conformational abnormalities, being ubiquitously found in amyloid deposits in Alzheimer's disease, dialysis-related amyloidosis and Parkinson's diseases. Human fibrinogen, an extracellular chaperone, was reported to specifically interact with a wide spectrum of stressed proteins and suppress their aggregation, being an interacting protein with TTR. Fibrinogen is differentially glycated in ATTR, leading to its chaperone activity loss. Here we show the existence of a proteostasis imbalance inATTRlinked to fibrinogen glycation by methylglyoxal.

Original languageEnglish
Pages (from-to)2225-2237
Number of pages13
JournalBiochemical Journal
Issue number14
Publication statusPublished - 2016


  • Chaperone
  • Fibrinogen
  • Glycation
  • Methylglyoxal
  • Transthyretin amyloidosis (ATTR)


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