Molecular Mechanism of Pathogenesis and Treatment Strategies for AL Amyloidosis

Hidehiko Ikura, Jin Endo, Hiroki Kitakata, Hidenori Moriyama, Motoaki Sano, Keiichi Fukuda

Research output: Contribution to journalReview articlepeer-review

Abstract

In amyloid light-chain (AL) amyloidosis, small B-cell clones (mostly plasma cell clones) present in the bone marrow proliferate and secrete unstable monoclonal free light chains (FLCs), which form amyloid fibrils that deposit in the interstitial tissue, resulting in organ injury and dysfunction. AL amyloidosis progresses much faster than other types of amyloidosis, with a slight delay in diagnosis leading to a marked exacerbation of cardiomyopathy. In some cases, the resulting heart failure is so severe that chemotherapy cannot be administered, and death sometimes occurs within a few months. To date, many clinical studies have focused on therapeutics, especially chemotherapy, to treat this disease. Because it is necessary to promptly lower FLC, the causative protein of amyloid, to achieve a hematological response, various anticancer agents targeting neoplastic plasma cells are used for the treatment of this disease. In addition, many basic studies using human specimens to elucidate the pathophysiology of AL have been conducted. Gene mutations associated with AL, the characteristics of amyloidogenic LC, and the structural specificity of amyloid fibrils have been clarified. Regarding the mechanism of cellular and tissue damage, the mass effect due to amyloid deposition, as well as the toxicity of pre-fibrillar LC, is gradually being elucidated. This review outlines the pathogenesis and treatment strategies for AL amyloidosis with respect to its molecular mechanisms.

Original languageEnglish
Article number6336
JournalInternational journal of molecular sciences
Volume23
Issue number11
DOIs
Publication statusPublished - 2022 Jun 1

Keywords

  • amyloid light-chain (AL) amyloidosis
  • chemotherapy
  • misfolded proteins
  • molecular mechanism
  • monoclonal free light chains (FLCs)

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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