Amyloid formation in light chain amyloidosis

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Light chain amyloidosis is one of the unique examples within amyloid diseases where the amyloidogenic precursor is a protein that escapes the quality control machinery and is secreted from the cells to be circulated in the bloodstream. The immunoglobulin light chains are produced by an abnormally proliferative monoclonal population of plasma cells that under normal conditions produce immunoglobulin molecules such as IgG, IgM or IgA. Once the light chains are in circulation, the proteins misfold and deposit as amyloid fibrils in numerous tissues and organs, causing organ failure and death. While there is a correlation between the thermodynamic stability of the protein and the kinetics of amyloid formation, we have recently found that this correlation applies within a thermodynamic range, and it is only a helpful correlation when comparing mutants from the same protein. Light chain amyloidosis poses unique challenges because each patient has a unique protein sequence as a result of the selection of a germline gene and the incorporation of somatic mutations. The exact location of the misfolding process is unknown as well as the full characterization of all of the toxic species populated during the amyloid formation process in light chain amyloidosis.

Original languageEnglish (US)
Pages (from-to)2523-2533
Number of pages11
JournalCurrent Topics in Medicinal Chemistry
Volume12
Issue number22
DOIs
StatePublished - 2012

Fingerprint

Amyloidosis
Amyloid
Light
Thermodynamics
Immunoglobulin Light Chains
Amyloidogenic Proteins
Proteins
Protein Stability
Poisons
Mutant Proteins
Plasma Cells
Quality Control
Immunoglobulin A
Immunoglobulin M
Immunoglobulins
Immunoglobulin G
Mutation
Population
Genes

Keywords

  • Amyloid formation
  • Dimer
  • Immunoglobulin light chain
  • Light chain amyloidosis
  • Somatic mutations

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Amyloid formation in light chain amyloidosis. / Ramirez-Alvarado, Marina.

In: Current Topics in Medicinal Chemistry, Vol. 12, No. 22, 2012, p. 2523-2533.

Research output: Contribution to journalArticle

@article{3f7a5b579bd04a5b97cce8967505739c,
title = "Amyloid formation in light chain amyloidosis",
abstract = "Light chain amyloidosis is one of the unique examples within amyloid diseases where the amyloidogenic precursor is a protein that escapes the quality control machinery and is secreted from the cells to be circulated in the bloodstream. The immunoglobulin light chains are produced by an abnormally proliferative monoclonal population of plasma cells that under normal conditions produce immunoglobulin molecules such as IgG, IgM or IgA. Once the light chains are in circulation, the proteins misfold and deposit as amyloid fibrils in numerous tissues and organs, causing organ failure and death. While there is a correlation between the thermodynamic stability of the protein and the kinetics of amyloid formation, we have recently found that this correlation applies within a thermodynamic range, and it is only a helpful correlation when comparing mutants from the same protein. Light chain amyloidosis poses unique challenges because each patient has a unique protein sequence as a result of the selection of a germline gene and the incorporation of somatic mutations. The exact location of the misfolding process is unknown as well as the full characterization of all of the toxic species populated during the amyloid formation process in light chain amyloidosis.",
keywords = "Amyloid formation, Dimer, Immunoglobulin light chain, Light chain amyloidosis, Somatic mutations",
author = "Marina Ramirez-Alvarado",
year = "2012",
doi = "10.2174/1568026611212220007",
language = "English (US)",
volume = "12",
pages = "2523--2533",
journal = "Current Topics in Medicinal Chemistry",
issn = "1568-0266",
publisher = "Bentham Science Publishers B.V.",
number = "22",

}

TY - JOUR

T1 - Amyloid formation in light chain amyloidosis

AU - Ramirez-Alvarado, Marina

PY - 2012

Y1 - 2012

N2 - Light chain amyloidosis is one of the unique examples within amyloid diseases where the amyloidogenic precursor is a protein that escapes the quality control machinery and is secreted from the cells to be circulated in the bloodstream. The immunoglobulin light chains are produced by an abnormally proliferative monoclonal population of plasma cells that under normal conditions produce immunoglobulin molecules such as IgG, IgM or IgA. Once the light chains are in circulation, the proteins misfold and deposit as amyloid fibrils in numerous tissues and organs, causing organ failure and death. While there is a correlation between the thermodynamic stability of the protein and the kinetics of amyloid formation, we have recently found that this correlation applies within a thermodynamic range, and it is only a helpful correlation when comparing mutants from the same protein. Light chain amyloidosis poses unique challenges because each patient has a unique protein sequence as a result of the selection of a germline gene and the incorporation of somatic mutations. The exact location of the misfolding process is unknown as well as the full characterization of all of the toxic species populated during the amyloid formation process in light chain amyloidosis.

AB - Light chain amyloidosis is one of the unique examples within amyloid diseases where the amyloidogenic precursor is a protein that escapes the quality control machinery and is secreted from the cells to be circulated in the bloodstream. The immunoglobulin light chains are produced by an abnormally proliferative monoclonal population of plasma cells that under normal conditions produce immunoglobulin molecules such as IgG, IgM or IgA. Once the light chains are in circulation, the proteins misfold and deposit as amyloid fibrils in numerous tissues and organs, causing organ failure and death. While there is a correlation between the thermodynamic stability of the protein and the kinetics of amyloid formation, we have recently found that this correlation applies within a thermodynamic range, and it is only a helpful correlation when comparing mutants from the same protein. Light chain amyloidosis poses unique challenges because each patient has a unique protein sequence as a result of the selection of a germline gene and the incorporation of somatic mutations. The exact location of the misfolding process is unknown as well as the full characterization of all of the toxic species populated during the amyloid formation process in light chain amyloidosis.

KW - Amyloid formation

KW - Dimer

KW - Immunoglobulin light chain

KW - Light chain amyloidosis

KW - Somatic mutations

UR - http://www.scopus.com/inward/record.url?scp=84874869909&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874869909&partnerID=8YFLogxK

U2 - 10.2174/1568026611212220007

DO - 10.2174/1568026611212220007

M3 - Article

C2 - 23339305

AN - SCOPUS:84874869909

VL - 12

SP - 2523

EP - 2533

JO - Current Topics in Medicinal Chemistry

JF - Current Topics in Medicinal Chemistry

SN - 1568-0266

IS - 22

ER -