Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Golgi-Associated plant Pathogenesis Related protein 1 (GAPR-1) is a mammalian protein that is a member of the Cysteine-rich secretory proteins, Antigen 5 and Pathogenesis related proteins group 1 (CAP) superfamily of proteins. A role for the common CAP domain in the function of the diverse superfamily members has not been described so far. Here, we show by a combination of independent techniques including electron microscopy, Thioflavin T fluorescence, and circular dichroism that GAPR-1 has the capability to form amyloid-like fibrils in the presence of liposomes containing negatively charged lipids. ⋯ Immuno-dot blot analysis revealed that GAPR-1 binds to prefibrillar oligomeric Aβ structures during the early stages of fibril formation. Another CAP domain-containing protein, CRISP2, was also capable of forming fibrils, indicating that oligomerization and fibril formation is a shared characteristic between CAP family members. We suggest that the CAP domain may regulate protein oligomerization in a large variety of proteins that define the CAP superfamily.
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To describe histological, immunohistochemical and ultrastructural features of synovial biopsies of amyloid arthropathy associated with multiple myeloma (MM). ⋯ This first detailed immunohistological analysis of MM-associated amyloid arthropathy suggests that it is a chronic synovitis that evolves despite the loss of humoral immunity seen in advanced MM. Instead, amyloid phagocytosis by synovial macrophages likely triggers and perpetuates local disease.
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Determine the role of phagocytosis in the deposition of acute phase SAA protein in peripheral organs as AA amyloid. ⋯ Macrophages have been shown to be instrumental in both accumulation and clearance of AA amyloid after cessation of inflammation. Our data indicate that when SAA protein is continuously present, depletion of phagocytic cells during the early course of the disease progression temporarily reduces amyloid load.
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Heterogeneity in the genotype-phenotype correlation of transthyretin (TTR)-related amyloidosis has been reported, suggesting that other factors may interact with disease-causing mutations. Additional genetic variants in the TTR gene and its surrounding regions may influence disease phenotype. To explore this hypothesis, we analyzed the TTR variation among human populations to identify functional inter-ethnic differences that could influence the TTR-related amyloidosis. ⋯ Our results highlighted that cis-regulatory variants may contribute to the cardiac TTR-related amyloidosis observed in patients carrier of Val122Ile mutation, the most common in population with African origin. Indeed, non-coding variants differentiated in Africans are, in some cases, located in binding sites of transcription factors involved in cardiac development and function (i.e. E2F3_2, REST, and TEAD).
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Familial amyloid polyneuropathy (FAP) mainly targets the peripheral nervous system and heart. Early noninvasive detection of cardiac impairment is critical for therapeutic management. ⋯ In FAP, NT-proBNP was associated with cardiac impairment suggesting that NT-proBNP could be used in carriers or in FAP patients with only neurologic symptoms for identifying the appropriate time to start cardiac echocardiographic assessment and follow-up. cTnT identified patients with severe cardiac disease.