Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Mounting evidence points to soluble peptide oligomers as the primary agents in various amyloid and prion diseases. Multiple mechanisms appear to contribute to the cytotoxic effects of these oligomers. Here, an additional, general mechanism is proposed - that soluble amyloid peptide oligomers serve as "all-purpose"beta strands that can interact with transiently unfolded or nascent proteins where interior beta-sheet edges are exposed. ⋯ If the bound amyloid oligomer dissociates at some point after the misfolded protein is committed to the UPS pathway, the oligomer could then repeat the process, adding a catalytic aspect to the misfolding mechanism. Direct proof of this proposed mechanism requires detection of amyloid oligomer-beta-sheet protein complexes, and a co-immunoprecipitation experiment is proposed. This hypothesis supports therapies that increase amyloid oligomer degradation or sequestration, as well as therapies that upregulate chaperone activity, for combating amyloid-related diseases.
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We report three patients with AL amyloidosis manifesting as systemic lymphadenopathy, mainly in the cervical and supraclavicular regions. Histopathology of lymph nodes showed massive deposition of AL amyloid with no abnormal findings suggestive of lymphoproliferative disorders. ⋯ The remaining patient showed no obvious change in the size of lymph nodes or detectable M-protein in serum. The prognosis of AL amyloidosis manifesting as lymphadenopathy is usually good as long as there are no hematological malignancies or rapid increases in the size of lymph nodes, but in cases of the systemic type, intensive chemotherapy, such as high-dose melphalan with auto-PBSCT, should be actively considered in order to avoid possible involvement of visceral organs.
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Familial transthyretin amyloidosis (ATTR), caused by mutant transthyretin deposition, is mainly characterized by peripheral neuropathy, autonomic dysfunction, and cardiomyopathy. There are few reports among the Chinese population. We previously described the TTR mutation (Val30Ala) in the first Hong Kong Chinese family with ATTR. ⋯ We performed DNA analysis in 46 subjects and detected a total of 21 patients, including the four probands, affected with ATTR, 15 of whom were still at a symptom-free stage at the time of writing. We conclude that ATTR remains largely underdiagnosed in the Chinese population. A high clinical suspicion is crucial for a timely diagnosis and can thus lead to a significant decrease in morbidity and mortality.
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To address whether or not the rarity of amyloidosis in Greek patients with rheumatoid arthritis (RA) is related to specific alleles of single nucleotide polymorphisms (SNPs) in the 5'-flanking region and the exon 3 of the SSA1 gene. ⋯ In conclusion, the rarity of the putative amyloidogenic -13T allele in Greek populations may be related to low prevalence of AA amyloidosis development in Greek RA patients.
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Hereditary fibrinogen amyloidosis is characterized by deposition of amyloid fibrils in renal glomeruli. The subunit protein of the amyloid fibrils is a proteolytic fragment of the fibrinogen Aalpha-chain. ⋯ We have carried out a full structural characterization of amyloid fibrils taken from disease tissue. These studies revealed that ex vivo fibrinogen amyloid fibrils have a cross-beta structure similar to other chemical types of amyloid fibrils.