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Amyloid: Morphology and Toxicity

  • Anders Olofsson , Johan Östman and Erik Lundgren
Published/Copyright: June 1, 2005
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Volume 40 Issue 12

Abstract

We have expressed transthyretin (TTR) mutants which have significantly destabilised tetramers that aggregate into amyloid fibrils via a series of intermediates. We used atomic force microscopy to follow the morphology of aggregates during fibril formation. Initially, amorphous aggregates are formed that subsequently mature into fibrillar structures. This observation is interpreted as an optimisation of β-strand registers. The rate of aggregation and maturation is highly temperature-dependent suggesting that entropic forces significantly contribute to stability. In addition, we identified a correlation between the presence of early formed aggregates of TTR and cytotoxicity. The toxic response was mediated via an apoptotic mechanism. The fact that early formed amorphous aggregates, but not more mature fibrils, exert a toxic response suggests that the rate of fibril formation may be a critical parameter. We propose that a slow rate of aggregation facilitates an increased concentration of a toxic intermediate.

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Published Online: 2005-06-01
Published in Print: 2002-12-10

Copyright © 2002 by Walter de Gruyter GmbH & Co. KG

Articles in the same Issue

  1. Author Index
  2. Subject Index
  3. Contents
  4. Historical Aspects and Perspectives in Transthyretin Research
  5. Transthyretin from Discovery to Now
  6. The Evolution of Transthyretin Synthesis in Vertebrate Liver, in Primitive Eukaryotes and in Bacteria
  7. The Evolution of Transthyretin Synthesis in the Choroid Plexus
  8. Hepatic Synthesis, Maturation and Complex Formation between Retinol-Binding Protein and Transthyretin
  9. Synthesis and Structural Analysis of the N-Terminal Domain of the Thyroid Hormone-Binding Protein Transthyretin
  10. Three-Dimensional Structure of the Transthyretin-Retinol-Binding Protein Complex
  11. Mechanisms of Molecular Recognition: Crystal Structure Analysis of Human and Rat Transthyretin Inhibitor Complexes
  12. Transthyretin in Fish: State of the Art
  13. The Effects of Endocrine-Disrupting Chemicals on Thyroid Hormone Binding to Xenopus laevis Transthyretin and Thyroid Hormone Receptor
  14. Clinical Picture and Outcome of Transthyretin-Related Familial Amyloid Polyneuropathy (FAP) in Japanese Patients
  15. Laboratory Assessment of Transthyretin Amyloidosis
  16. Amyloid: Morphology and Toxicity
  17. Historical Overview of Analytical Methods for the Measurement of Transthyretin
  18. Nutritional Regulation of Visceral Markers in Rat Liver and Cultured Hepatoma Cells
  19. Significance of Transthyretin in Protein Metabolism
  20. Transthyretin as a Thyroid Hormone Carrier: Function Revisited
  21. The Molar Ratio of Retinol-Binding Protein to Transthyretin in the Assessment of Vitamin A Status in Adults. Proposal of a Cut-off Point
  22. Observations with Regard to the National Kidney Foundation K/DOQI Clinical Practice Guidelines Concerning Serum Transthyretin in Chronic Renal Failure
  23. Metabolism and Clinical Interest of Serum Transthyretin (Prealbumin) in Dialysis Patients
  24. Protein Status in Pancreatitis – Transthyretin Is a Sensitive Biomarker of Malnutrition in Acute and Chronic Pancreatitis
  25. Assessment of Nutritional Status in Organ Transplant: Is Transthyretin a Reliable Indicator?
  26. Body Composition and Nutritional Parameters in HIV and AIDS Patients
  27. C-Reactive Protein to Transthyretin Ratio for the Early Diagnosis and Follow-up of Postoperative Infection
  28. The Prognostic Value of Nutritional and Inflammatory Indices in Critically Ill Patients with Acute Respiratory Failure
  29. Transthyretin: Its Response to Malnutrition and Stress Injury. Clinical Usefulness and Economic Implications
  30. Transthyretin Measurement as a Screening Tool for Protein Calorie Malnutrition in Emergency Hospital Admissions
  31. Outcomes of Continuous Process Improvement of a Nutritional Care Program Incorporating TTR Measurement
  32. The Role of Visceral Protein Markers in Protein Calorie Malnutrition
  33. Acknowledgement
  34. Meetings
https://doi.org/10.1515/CCLM.2002.219

Articles in the same Issue

  1. Author Index
  2. Subject Index
  3. Contents
  4. Historical Aspects and Perspectives in Transthyretin Research
  5. Transthyretin from Discovery to Now
  6. The Evolution of Transthyretin Synthesis in Vertebrate Liver, in Primitive Eukaryotes and in Bacteria
  7. The Evolution of Transthyretin Synthesis in the Choroid Plexus
  8. Hepatic Synthesis, Maturation and Complex Formation between Retinol-Binding Protein and Transthyretin
  9. Synthesis and Structural Analysis of the N-Terminal Domain of the Thyroid Hormone-Binding Protein Transthyretin
  10. Three-Dimensional Structure of the Transthyretin-Retinol-Binding Protein Complex
  11. Mechanisms of Molecular Recognition: Crystal Structure Analysis of Human and Rat Transthyretin Inhibitor Complexes
  12. Transthyretin in Fish: State of the Art
  13. The Effects of Endocrine-Disrupting Chemicals on Thyroid Hormone Binding to Xenopus laevis Transthyretin and Thyroid Hormone Receptor
  14. Clinical Picture and Outcome of Transthyretin-Related Familial Amyloid Polyneuropathy (FAP) in Japanese Patients
  15. Laboratory Assessment of Transthyretin Amyloidosis
  16. Amyloid: Morphology and Toxicity
  17. Historical Overview of Analytical Methods for the Measurement of Transthyretin
  18. Nutritional Regulation of Visceral Markers in Rat Liver and Cultured Hepatoma Cells
  19. Significance of Transthyretin in Protein Metabolism
  20. Transthyretin as a Thyroid Hormone Carrier: Function Revisited
  21. The Molar Ratio of Retinol-Binding Protein to Transthyretin in the Assessment of Vitamin A Status in Adults. Proposal of a Cut-off Point
  22. Observations with Regard to the National Kidney Foundation K/DOQI Clinical Practice Guidelines Concerning Serum Transthyretin in Chronic Renal Failure
  23. Metabolism and Clinical Interest of Serum Transthyretin (Prealbumin) in Dialysis Patients
  24. Protein Status in Pancreatitis – Transthyretin Is a Sensitive Biomarker of Malnutrition in Acute and Chronic Pancreatitis
  25. Assessment of Nutritional Status in Organ Transplant: Is Transthyretin a Reliable Indicator?
  26. Body Composition and Nutritional Parameters in HIV and AIDS Patients
  27. C-Reactive Protein to Transthyretin Ratio for the Early Diagnosis and Follow-up of Postoperative Infection
  28. The Prognostic Value of Nutritional and Inflammatory Indices in Critically Ill Patients with Acute Respiratory Failure
  29. Transthyretin: Its Response to Malnutrition and Stress Injury. Clinical Usefulness and Economic Implications
  30. Transthyretin Measurement as a Screening Tool for Protein Calorie Malnutrition in Emergency Hospital Admissions
  31. Outcomes of Continuous Process Improvement of a Nutritional Care Program Incorporating TTR Measurement
  32. The Role of Visceral Protein Markers in Protein Calorie Malnutrition
  33. Acknowledgement
  34. Meetings
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