ArticleBiochemistry2009
The 8 and 5 kDa fragments of plasma gelsolin form amyloid fibrils by a nucleated polymerization mechanism, while the 68 kDa fragment is not amyloidogenic.
Article in Biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 42 citations in OpenAlex.
- A molecular perspective of gelsolin amyloidosis: An old foe with new faces.Cellular and molecular life sciences : CMLS · 2026Review
- Renal gelsolin amyloidosis as a rare cause of proteinuria: a case report and literature review.BMC nephrology · 2025Review
- Plant Hormone Cytokinin as Aggregation Modulator of Gelsolin Amyloidosis.Journal of peptide science : an official publication of the European Peptide Society · 2025Article
- Development of an in vitro aggregation assay for long synthetic polypeptide, amyloidogenic gelsolin fragment AGelD187N 173-242.PloS one · 2023Article
- Rational Design of a Peptidomimetic Inhibitor of Gelsolin Amyloid Aggregation.International journal of molecular sciences · 2022Article
- Uncovering the universality of self-replication in protein aggregation and its link to disease.Science advances · 2022Article
- Aggregation of gelsolin wild-type and G167K/R, N184K, and D187N/Y mutant peptides and inhibition.Molecular and cellular biochemistry · 2021Article
- A novel hotspot of gelsolin instability triggers an alternative mechanism of amyloid aggregation.Computational and structural biotechnology journal · 2021Article
- The structure of N184K amyloidogenic variant of gelsolin highlights the role of the H-bond network for protein stability and aggregation properties.European biophysics journal : EBJ · 2020Article
- Gelsolin pathogenic Gly167Arg mutation promotes domain-swap dimerization of the protein.Human molecular genetics · 2018Article
- Molecular basis of a novel renal amyloidosis due to N184K gelsolin variant.Scientific reports · 2016Article
- Article
- Chaperone nanobodies protect gelsolin against MT1-MMP degradation and alleviate amyloid burden in the gelsolin amyloidosis mouse model.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Immunoprecipitation of amyloid fibrils by the use of an antibody that recognizes a generic epitope common to amyloid fibrils.PloS one · 2014Article
- Active Achilles tendon kinesitherapy accelerates Achilles tendon repair by promoting neurite regeneration.Neural regeneration research · 2012Article
- Heparin binds 8 kDa gelsolin cross-β-sheet oligomers and accelerates amyloidogenesis by hastening fibril extension.Biochemistry · 2011Article
- Gelsolin amyloidosis: genetics, biochemistry, pathology and possible strategies for therapeutic intervention.Critical reviews in biochemistry and molecular biologyReview
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7 authors.
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Abstract
Familial amyloidosis of Finnish type (FAF), or gelsolin amyloidosis, is a systemic amyloid disease caused by a mutation (D187N/Y) in domain 2 of human plasma gelsolin, resulting in domain 2 misfolding within the secretory pathway. When D187N/Y gelsolin passes through the Golgi, furin endoproteolysis within domain 2 occurs as a consequence of the abnormal conformations that enable furin to bind and cleave, resulting in the secretion of a 68 kDa C-terminal fragment (amino acids 173-755, C68). The C68 fragment is cleaved upon secretion from the cell by membrane type 1 matrix metalloprotease (MT1-MMP), affording the 8 and 5 kDa fragments (amino acids 173-242 and 173-225, respectively) comprising the amyloid fibrils in FAF patients. Herein, we show that the 8 and 5 kDa gelsolin fragments form amyloid fibrils by a nucleated polymerization mechanism. In addition to demonstrating the expected concentration dependence of a nucleated polymerization reaction, the addition of preformed amyloid fibrils, or "seeds", was shown to bypass the requirement for the formation of a high-energy nucleus, accelerating 8 and 5 kDa D187N gelsolin amyloidogenesis. The C68 fragment can form small oligomers, but not amyloid fibrils, even when seeded with preformed 8 kDa fragment plasma gelsolin fibrils. Because the 68 kDa fragment of gelsolin does not form amyloid fibrils in vitro or in a recently published transgenic mouse model of FAF, we propose that administration of an MT1-MMP inhibitor could be an effective strategy for the treatment of FAF.
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