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 journalArticle

3 Citations (Scopus)

Abstract

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
Volume473
Issue number14
DOIs
Publication statusPublished - 2016

Fingerprint

Pyruvaldehyde
Amyloid
Fibrinogen
Prealbumin
Amyloid Plaques
Proteostasis Deficiencies
Advanced Glycosylation End Products
Proteins
Deposits
Agglomeration
Peripheral Nervous System
Amyloidosis
Parkinson Disease
Dialysis
Consensus
Alzheimer Disease
Neurology

Keywords

  • Chaperone
  • Fibrinogen
  • FTICR-MS
  • Glycation
  • Methylglyoxal
  • Transthyretin amyloidosis (ATTR)

Cite this

Fonseca, D., Gilberto, S., Ribeiro-Silva, C., Ribeiro, R., Guinote, I. B., Saraiva, S., ... Da Costa, G. (2016). The role of fibrinogen glycation in ATTR: Evidence for chaperone activity loss in disease. Biochemical Journal, 473(14), 2225-2237. https://doi.org/10.1042/BCJ20160290
Fonseca, Daniel ; Gilberto, Samuel ; Ribeiro-Silva, Cristina ; Ribeiro, Raquel ; Guinote, Ines Batista ; Saraiva, Susana ; Gomes, Ricardo Jorge ; Mateus, Elia ; Viana, Ana S. ; Barroso, Eduardo ; Freire, Ana Ponces ; Freire, Patrick ; Cordeiro, Carlos ; Da Costa, Goncalo. / The role of fibrinogen glycation in ATTR : Evidence for chaperone activity loss in disease. In: Biochemical Journal. 2016 ; Vol. 473, No. 14. pp. 2225-2237.
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abstract = "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.",
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Fonseca, D, Gilberto, S, Ribeiro-Silva, C, Ribeiro, R, Guinote, IB, Saraiva, S, Gomes, RJ, Mateus, E, Viana, AS, Barroso, E, Freire, AP, Freire, P, Cordeiro, C & Da Costa, G 2016, 'The role of fibrinogen glycation in ATTR: Evidence for chaperone activity loss in disease', Biochemical Journal, vol. 473, no. 14, pp. 2225-2237. https://doi.org/10.1042/BCJ20160290

The role of fibrinogen glycation in ATTR : Evidence for chaperone activity loss in disease. / Fonseca, Daniel; Gilberto, Samuel; Ribeiro-Silva, Cristina; Ribeiro, Raquel; Guinote, Ines Batista; Saraiva, Susana; Gomes, Ricardo Jorge; Mateus, Elia; Viana, Ana S.; Barroso, Eduardo; Freire, Ana Ponces; Freire, Patrick; Cordeiro, Carlos; Da Costa, Goncalo.

In: Biochemical Journal, Vol. 473, No. 14, 2016, p. 2225-2237.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The role of fibrinogen glycation in ATTR

T2 - Evidence for chaperone activity loss in disease

AU - Fonseca, Daniel

AU - Gilberto, Samuel

AU - Ribeiro-Silva, Cristina

AU - Ribeiro, Raquel

AU - Guinote, Ines Batista

AU - Saraiva, Susana

AU - Gomes, Ricardo Jorge

AU - Mateus, Elia

AU - Viana, Ana S.

AU - Barroso, Eduardo

AU - Freire, Ana Ponces

AU - Freire, Patrick

AU - Cordeiro, Carlos

AU - Da Costa, Goncalo

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

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KW - FTICR-MS

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