Molecular Mechanisms of Amyloidosis
New England Journal of MedicinePublished 7 August 2003
Giampaolo Merlini, Vittorio Bellotti
Citations1,870
SJR quartileQ1
SJR score19.08
SNIP13.47
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TL;DR
The molecular basis of various types of amyloidosis is reviewed and new ways of treating these disorders are proposed.
Abstract
Amyloidosis affects millions of people, as a cause of Alzheimer's disease or a complication of dialysis, and also causes rare conditions. The many forms of the disorder have one underlying principle: misfolded proteins. Prompt, correct diagnosis is essential, especially in the inherited forms of amyloidosis. This article reviews the molecular basis of various types of amyloidosis and proposes new ways of treating these disorders.
Keywords
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The aim of the present study is to evaluate the survival of the initial group of unselected liver transplant recipients with FAP, a dominantly inherited neuropathic amyloidosis caused by a mutant transthyretin.
PubMedCharacterization of tissue and plasma glycosaminoglycans during experimental AA amyloidosis and acute inflammation. Qualitative and quantitative analysis.
81 Citations1987Alan D. Snow, Robert Kisilevsky +2 more
The results suggest that GAG metabolism, in particular heparin/heparan sulfate, are intimately involved in the process of AA amyloidogenesis.
Biochemical and Biophysical Research CommunicationsComparative Studies of Two Transthyretin Variants with Protective Effects on Familial Amyloidotic Polyneuropathy: TTR R104H and TTR T119M
80 Citations2000Maria Rosário Almeida, Isabel L. Alves +3 more
The results indicate that the His 104 substitution induces structural alterations that increase the stability of the tetramer in compound heterozygotes for TTR M30 despite a lower affinity for T(4) binding.
Nature Structural BiologyIlluminating folding intermediates.
79 Citations2000Christian Schultz
Time-resolved Fourier transform infrared spectroscopy provides evidence of non-native antiparallel β-sheet structural elements in the folding intermediates of α-lactalbumin.
British Journal of HaematologyA modified high‐dose dexamethasone regimen for primary systemic (AL) amyloidosis
77 Citations2001Giovanni Palladini, Ernesto Anesi +6 more
The preliminary experience with the usual HD‐Dex schedule indicated that the induction phase was rather toxic in AL patients, so a milder schedule consisting of dexamethasone 40’mg on d’1–4 q21’d for up to eight cycles was adopted.
Clinical Immunology and ImmunopathologyPreferential Expression of Human λ-Light-Chain Variable-Region Subgroups in Multiple Myeloma, AL Amyloidosis, and Waldenström's Macroglobulinemia
74 Citations1994Shuji Ozaki, Masahiro Abe +3 more
The finding that certain V lambda subgroups are nonstochastically expressed in lambda-type multiple myeloma, AL amyloidosis, and Waldenström's macroglobulinemia provides evidence for abnormal VL gene usage in these disorders and, thus, furnishes new insight into their pathogenesis.
TransplantationCLINICAL AND BIOCHEMICAL OUTCOME OF HEPATORENAL TRANSPLANTATION FOR HEREDITARY SYSTEMIC AMYLOIDOSIS ASSOCIATED WITH APOLIPOPROTEIN AI Gly26Arg1
70 Citations2001Julian D. Gillmore, Arie J. Stangou +8 more
Plasma levels of variant apoAI decreased by 50% after liver transplantation, and the patient was asymptomatic 2 years after surgery, which supports the use of liver transplants in patients with hereditary apolipoprotein AI amyloidosis who develop hepatic dysfunction.
AmyloidLight and electron microscopy immunohistochemical characterization of amyloid deposits
63 Citations1997Eloisa Arbustini, Patrizia Morbini +8 more
The present study reports optimized fixation and processing methods for the light and electron microscopic immunohistochemical characterization of tissue amyloid characterization in abdominal fat aspirates and tissue biopsy samples from different organs from 36 patients.
AmyloidA multicenter phase II trial of 4′-iodo-4′-deoxydoxorubicin (IDOX) in primary amyloidosis (AL)
62 Citations2002Morie A. Gertz, Martha Q. Lacy +7 more
IDOX administered in this protocol was insufficiently active at the current dose, and 12 of the patients have died.
American Journal Of Pathology4′-Iodo-4′-Deoxydoxorubicin Disrupts the Fibrillar Structure of Transthyretin Amyloid
60 Citations2000Joana Almeida Palha, Dario Ballinari +6 more
The hypothesis that I-DOX and less toxic derivatives can prove efficient in the treatment of TTR-related amyloidosis is supported.
BloodEvidence That Amyloidogenic Light Chains Undergo Antigen-Driven Selection
57 Citations1998Vittorio Perfetti, Paola Ubbiali +9 more
Analysis of the nature and distribution of somatic mutations in amyloid V regions showed that there was statistical evidence of antigen selection in 8 of 14 clones, indicating that a substantial proportion of the amyloids clones developed from B cells selected for improved antigen binding properties and that pathogenic light chains show evidence of this selection.
Proceedings of the National Academy of SciencesEquilibria and kinetics of folding of gelsolin domain 2 and mutants involved in familial amyloidosis–Finnish type
53 Citations1999Rivka L. Isaacson, Alan G. Weeds +1 more
The destabilization conferred on gelsolin domain 2 by the FAF mutations is sufficient to predict that an appreciable fraction is unfolded and, therefore, extremely susceptible to proteolysis at body temperature.
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