Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease.
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ABSTRACT:
SUBMITTER: Zhang B
PROVIDER: S-EPMC2377313 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AA amyloidosis is a protein misfolding disease characterized by extracellular deposition of amyloid A (AA) fibrils. AA amyloidosis has been identified in food animals, and it has been postulated that AA amyloidosis may be transmissible to different animal species. Since the precursor protein of AA fibrils is serum amyloid A (SAA), which is an inflammatory acute phase protein, AA amyloidosis is considered to be associated with inflammatory diseases such as rheumatoid arthritis. Chronic diseases such as autoimmune disease and type 2 diabetes mellitus could be potential factors for AA amyloidosis. In this study, to examine the relationship between the induction of AA amyloidosis and chromic abnormalities such as autoimmune disease or type 2 diabetes mellitus, amyloid fibrils from mice, cattle, or chickens were experimentally injected into disease model mice. Wild-type mice were used as controls. The concentrations of SAA, IL-6, and IL-10 in autoimmune disease model mice were higher than those of control mice. However, induction of AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice was lower than that in control mice, and the amount of amyloid deposits in the spleens of both mouse models was lower than that of control mice according to Congo red staining and immunohistochemistry. These results suggest that factors other than SAA levels, such as an inflammatory or anti-inflammatory environment in the immune response, may be involved in amyloid deposition.
| S-EPMC5111846 | biostudies-literature
Project description:Amyloid A (AA) amyloidosis is a lethal disease characterized by systemic AA amyloid deposition, and is reported in many animal species. Despite experiments have shown that AA amyloidosis can be transmitted orally, horizontal transmission and cross-species transmission are concerns, the transmission mechanism has been unknown. In this study, we examined the oral transmission efficiency of AA amyloidosis using oxazolone-induced gastrointestinal disorder mice. As a result, the upper or lower gastrointestinal disorder groups developed more severe amyloid deposition in systemic tissues than the group without gastrointestinal disorders. The results of this study suggest that gastrointestinal damage promotes the oral transmission of AA amyloidosis.
| S-EPMC8267199 | biostudies-literature
Project description:In AA amyloidosis, cross-species oral transmission has been demonstrated in several animal models. While it is known that the transmission efficiency of AA amyloidosis between different species is lower than that among the same species, the mechanism of this species-barrier is unclear. In this study, we found at first that mice orally given a large amount of bovine AA simultaneously with inflammatory stimulation did not develop AA amyloidosis. Therefore, we hypothesized that the low efficiency of the cross-species oral transmission of AA amyloidosis might be due to the low absorption rate in Peyer's patches. To evaluate the hypothesis, we next investigated whether bovine AA was taken up by Peyer's patches and translocated to other organs in vivo and ex vivo models. The direct absorption of bovine AA by Peyer's patches was not observed. Besides, translocation of bovine AA to the mesenteric lymph nodes, spleen, liver, or kidney was not observed except the mesenteric lymph node of a single mouse. Thus, absorption of bovine AA by Peyer's patches occurred much less efficiently in mouse models of cross-species oral transmission of AA amyloidosis. The present study suggests that the less efficient amyloid uptake by Peyer's patches may be involved in the species-barrier of oral transmission of AA amyloidosis.
| S-EPMC8267202 | biostudies-literature
Project description:Secondary (AA) amyloidosis is a multisystem disorder complicating chronic infections or inflammatory diseases. It is characterized by extracellular deposit of fibrils composed of fragments of serum amyloid A (SAA), an acute phase reactant protein. The kidney is the most frequent organ involved, manifesting as progressive proteinuria and renal impairment. Attenuation of the level of circulating SAA protein by treating the underlying inflammatory condition remains the primary strategy in treating AA amyloidosis. However, at times, achieving adequate control of protein production can prove difficult. In addition, relapse of renal function often occurs rapidly following any subsequent inflammatory stimulus in patients with existing amyloidosis. Recently there has been an interest in finding other potential strategies targeting amyloid deposits themselves. Eprodisate is a sulfonated molecule with a structure similar to heparan sulfate. It competitively binds to the glycosaminoglycan-binding sites on SAA and inhibits fibril polymerization and amyloid deposition. Recent randomized clinical trial showed that it may slow down progressive renal failure in patients with AA amyloidosis. However confirmatory studies are needed and results of a second Phase III study are eagerly awaited to clarify whether or not eprodisate has a place in treating renal amyloid disease.
| S-EPMC3304340 | biostudies-other
Project description:The term "amyloidosis" encompasses the heterogeneous group of diseases caused by the extracellular deposition of autologous fibrillar proteins. The global incidence of amyloidosis is estimated at five to nine cases per million patient-years. While amyloid light-chain (AL) amyloidosis is more frequent in developed countries, amyloid A (AA) amyloidosis is more common in some European regions and in developing countries. The spectrum of AA amyloidosis has changed in recent decades owing to: an increase in the median age at diagnosis; a percent increase in the frequency of primary AL amyloidosis with respect to the AA type; and a substantial change in the epidemiology of the underlying diseases. Diagnosis of amyloidosis is based on clinical organ involvement and histological evidence of amyloid deposits. Among the many tinctorial characteristics of amyloid deposits, avidity for Congo red and metachromatic birefringence under unidirectional polarized light remain the gold standard. Once the initial diagnosis has been made, the amyloid subtype must be identified and systemic organ involvement evaluated. In this sense, the (123)I-labeled serum amyloid P component scintigraphy is a safe and noninvasive technique that has revolutionized the diagnosis and monitoring of treatment in systemic amyloidosis. It can successfully identify anatomical patterns of amyloid deposition throughout the body and enables not only an initial estimation of prognosis, but also the monitoring of the course of the disease and the response to treatment. Given the etiologic diversity of AA amyloidosis, common therapeutic strategies are scarce. All treatment options should be based upon a greater control of the underlying disease, adequate organ support, and treatment of symptoms. Nevertheless, novel therapeutic strategies targeting the formation of amyloid fibrils and amyloid deposition may generate new expectations for patients with AA amyloidosis.
| S-EPMC4218891 | biostudies-other
Project description:Amyloid A (AA) amyloidosis occurs spontaneously in many mammals and birds, but the prevalence varies considerably among different species, and even among subgroups of the same species. The Blue fox and the Gray fox seem to be resistant to the development of AA amyloidosis, while Island foxes have a high prevalence of the disease. Herein, we report on the identification of AA amyloidosis in the Red fox (Vulpes vulpes). Edman degradation and tandem MS analysis of proteolyzed amyloid protein revealed that the amyloid partly was composed of full-length SAA. Its amino acid sequence was determined and found to consist of 111 amino acid residues. Based on inter-species sequence comparisons we found four residue exchanges (Ser31, Lys63, Leu71, Lys72) between the Red and Blue fox SAAs. Lys63 seems unique to the Red fox SAA. We found no obvious explanation to how these exchanges might correlate with the reported differences in SAA amyloidogenicity. Furthermore, in contrast to fibrils from many other mammalian species, the isolated amyloid fibrils from Red fox did not seed AA amyloidosis in a mouse model.
| S-EPMC5654853 | biostudies-literature
Project description:Spongiform encephalopathies have been reported to be transmitted by blood transfusion even prior to the clinical onset. Experimental AA-amyloidosis shows similarities with prion disease and amyloid-containing organ-extracts can prime a recipient for the disease. In this systemic form of amyloidosis N-terminal fragments of the acute-phase reactant apolipoprotein serum amyloid A are the main amyloid protein. Initial amyloid deposits appear in the perifollicular region of the spleen, followed by deposits in the liver. We used the established murine model and induced AA-amyloidosis in NMRI mice by intravenous injections of purified amyloid fibrils ('amyloid enhancing factor') combined with inflammatory challenge (silver nitrate subcutaneously). Blood plasma and peripheral blood monocytes were isolated, sonicated and re-injected into new recipients followed by an inflammatory challenge during a three week period. When the animals were sacrificed presence of amyloid was analyzed in spleen sections after Congo red staining. Our result shows that some of the peripheral blood monocytes, isolated from animals with detectable amyloid, contained amyloid-seed that primed for AA-amyloid. The seeding material seems to have been phagocytosed by the cells since the AA-precursor (SAA1) was found not be expressed by the monocytes. Plasma recovered from mice with AA amyloidosis lacked seeding capacity. Amyloid enhancing activity can reside in monocytes recovered from mice with AA-amyloidosis and in a prion-like way trigger amyloid formation in conjunction with an inflammatory disorder. Human AA-amyloidosis resembles the murine form and every individual is expected to be exposed to conditions that initiate production of the acute-phase reactant. The monocyte-transfer mechanism should be eligible for the human disease and we point out blood transfusion as a putative route for transfer of amyloidosis.
| S-EPMC2553266 | biostudies-literature
Project description:Objective: Amyloid A (AA) amyloidosis is found in humans and non-human primates, but quantifying disease risk prior to clinical symptoms is challenging. We applied machine learning to identify the best predictors of amyloidosis in rhesus macaques from available clinical and pathology records. To explore potential biomarkers, we also assessed whether changes in circulating serum amyloid A (SAA) or lipoprotein profiles accompany the disease. Methods: We conducted a retrospective study using 86 cases and 163 controls matched for age and sex. We performed data reduction on 62 clinical, pathological and demographic variables, and applied multivariate modelling and model selection with cross-validation. To test the performance of our final model, we applied it to a replication cohort of 2,775 macaques. Results: The strongest predictors of disease were colitis, gastrointestinal adenocarcinoma, endometriosis, arthritis, trauma, diarrhoea and number of pregnancies. Sensitivity and specificity of the risk model were predicted to be 82%, and were assessed at 79 and 72%, respectively. Total, low density lipoprotein and high density lipoprotein cholesterol levels were significantly lower, and SAA levels and triglyceride-to-HDL ratios were significantly higher in cases versus controls. Conclusion: Machine learning is a powerful approach to identifying macaques at risk of AA amyloidosis, which is accompanied by increased circulating SAA and altered lipoprotein profiles.
| S-EPMC6667354 | biostudies-literature
Project description:We here report for the first time on the chemical characteristics of proteoglycans associated with mouse splenic reactive AA amyloid. Amyloid was induced in CBA/J mice by two different procedures; conventional casein treatment and by employing Freund's complete adjuvant, accelerated by Trypan Blue. Pulse-labelling was employed at distinct stages during amyloid development, followed by [35S]proteoglycan characterization of organ extracts. Repetitive 35S injections were also administered during the phase where amyloid deposition occurred most rapidly. Proteoglycans were extracted with guanidine in the presence of protease inhibitors and purified. The results showed that the production of proteoglycans is dramatically enhanced during amyloidogenesis, the glycosaminoglycan and proteoglycan accumulation being not only dependent on alterations in proteoglycan catabolism, but rather on increased synthesis. The increment could be demonstrated even at the stage before microscopic detection of amyloid deposits, clearly suggesting that the upregulation of proteoglycan expression precedes amyloid fibril formation. Two major proteoglycans were found to accumulate in advanced splenic amyloid; one a heparan sulphate proteoglycan of approx. 200 kDa with a core protein of 70 kDa, the other a chondroitin sulphate proteoglycan of smaller size. Moreover, free dermatan sulphate chains seemed to specifically accumulate in the organs during amyloid fibrillogenesis. We suggest that free glycosaminoglycans may be a specific feature of amyloidosis and that different proteoglycans and glycosaminoglycans play a role in formation and stabilization of amyloid fibrils in vivo.
| S-EPMC1137378 | biostudies-other
Project description:In the several types of amyloidoses, participation of oxidative stresses in the pathogenesis and the effect of antioxidants on amyloidosis have been reported. Meanwhile, the relationship between oxidative stresses and pathogenesis of amyloid A (AA) amyloidosis is still unclear. In this study, we used an antioxidant, Brazilian propolis, to investigate the inhibitory effects on AA amyloidosis. The results showed that AA deposition was inhibited by administration of propolis. Increased expression of antioxidant markers was detected in molecular biological examinations of mice treated with propolis. Although serum amyloid A (SAA) levels were strongly correlated with the immunoreactive area of AA deposits in the control group, the correlation was weaker in the propolis-treated groups. In addition, there were no changes in SAA levels between the control group and the propolis-treated groups. The results indicate that propolis, an antioxidant, may induce inhibitory effects against AA amyloidosis.
| S-EPMC5938209 | biostudies-literature