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Amyloid Diseases at the Molecular Level: General Overview and Focus on AL Amyloidosis

  • Mario Nuvolone
  • Giovanni Palladini
  • Giampaolo MerliniEmail author
Part of the Current Clinical Pathology book series (CCPATH)

Abstract

The amyloidoses encompass a heterogeneous group of diseases, wherein a misfolded protein accumulates extracellularly in the form of amyloid deposits, resulting in tissue damage and organ dysfunction.

Intrinsic instability, increased concentration, proteolytic cleavage and/or mutations of a precursor protein favour its conversion into an aggregation-prone misfolded state, which ultimately results in the formation of amyloid fibrils through poorly identified prefibrillar oligomeric species. The latter are believed to be the main culprit for the toxicity.

Numerous unrelated proteins can undergo this process, resulting in different types of the disease. Among these, systemic immunoglobulin light chain (AL) amyloidosis is caused by a usually small and nonproliferating plasma cell clone, which resides in the bone marrow and secretes an amyloidogenic light chain into the circulation. Almost any organ can be the site of amyloid deposition, rendering AL a truly protean condition.

The identification of a monoclonal component in a patient with histological evidence of amyloid disease is strongly suggestive, but not pathognomonic, of AL amyloidosis. Correct typing requires a scrupulous and multidisciplinary approach and forms the basis for an etiological therapy. Standard therapies aim at eradicating the amyloidogenic precursor, but novel complementary therapeutic approaches are under intense scrutiny.

Keywords

Amyloidosis Amyloid Protein misfolding Protein toxicity Oligomers Plasma cell dyscrasia 

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Mario Nuvolone
    • 1
    • 2
  • Giovanni Palladini
    • 3
  • Giampaolo Merlini
    • 3
    Email author
  1. 1.Institute of NeuropathologyUniversity Hospital of ZurichZurichSwitzerland
  2. 2.Amyloidosis Research and Treatment Center, Foundation Scientific Institute Policlinico San Matteo, Department of Molecular MedicineUniversity of PaviaPaviaItaly
  3. 3.Department of Molecular Medicine and Amyloidosis Research and Treatment CenterFoundation IRCCS Policlinico San Matteo and University of PaviaPaviaItaly

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