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Inhibition of serum amyloid A protein amyloid formation

100%

Sosnowska M., Jankowska E.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

The acute-phase protein serum amyloid A (SAA) is present in the bloodstream at the concentration below 1 µM under physiological conditions, but its level increases significantly during the acute-phase response following infection or inflammatory condition. A consequence of the long-term elevated SAA concentration is deposition of normally soluble serum amyloid A in the form of insoluble fibrils, impairing tissue structure and function. These deposits cause development of a secondary type amyloidosis, called amyloid A protein (AA) amyloidosis, which results in a death of thousands of people per annum around the world. The ability of SAA to form amyloids seems to be connected with the N-terminal portion of the molecule. The capacity of the synthetic peptides derived from the N-terminal sequence of human or mice SAA to form fibrils in vitro proves that the most amyloidogenic region is embedded within the protein’s first 15 amino acids. We decided therefore to use peptides consisting of 11–15 amino acids and the sequence derived from the N-terminus of the parent aggregating protein as a research tool for investigation of the molecular recognition and self-assembly mechanisms that promote the formation of SAA amyloid fibrils deposits. In this study, we tested the hypothesis that non-aggregating very short peptides derived from SAA sequence would interact with the analogous region in the protein molecule or its aggregation-prone N-terminal fragment, and block its assembly into oligomers and amyloid fibrils. We designed and synthesized a peptide with the sequence 1RSFFS5, derived from the human SAA primary structure, and then tested it as a potential inhibitor of the aggregation process of SAA protein. The hypothesis about the role of aromatic interactions in amyloid fibril formation led us to test another peptide: 17LVFF20, which is derived from the sequence of Aβ. We tested propensity of the N-terminal segment (1–15) of mice SAA for amyloid fibrils formation, incubating it either alone or together with the potential inhibitors. Thioflavin T (ThT) fluorescence test was used to detect amyloid fibrils formation. These tests confirmed that the designed peptides are able to diminish propensity of the aggregation-prone SAA peptides to form amyloid fibrils. There are currently no effective medical treatment of diseases associated with the systemic amyloidosis. We believe that results of the presented project open up new possibilities in designing compounds that are able to prevent formation of amyloid deposits and could be a starting point for the design of peptidomimetic molecules more suitable as potential drugs. The work was supported by grant NCN nr 2011/03/N/NZ5/01460 and grant BMN No 538-8440-1042-12.

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Cortical fibrils and secondary deposits in periderm of the hemichordate Rhabdopleura [Graptolithoidea]

100%

Mierzejewski P., Kulicki C.

Acta Palaeontologica Polonica

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2003

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tom 48

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nr 1

Coenecia of extant hemichordates Rhabdopleura compacta and Rh. normani were investigated using SEM techniques. Cortical fibrils were detected in their fusellar tissue for the first time. The densely packed cortical fibrils form a characteristic band−like construction in fusellar collars, similar to some Ordovician rhabdopleurids. No traces of external secondary deposits are found in coenecia. Two types of internal secondary deposits in tubes are recognized: (1) membranous deposits, composed of numerous, tightly packed sheets, similar to the crustoid paracortex and pseudocortex; and (2) fibrillar deposits, devoid(?) of sheets and made of cortical fibrils, arranged in parallel and interpreted as equivalent to graptolite endocortex. There is no significant difference in either the shape or the dimensions of cortical fibrils found in Rhabdopleura and graptolites. The cortical fabric of both rhabdopleuran species studied is composed of long, straight and more or less wavy, unbranched fibrils arranged in parallel; their diameters vary from 220 to 570 µm. The study shows that there is no significant difference between extinct and extant Graptolithoidea (= Pterobranchia) in the histological and ultrastructural pattern of their primary and secondary deposits of the periderm. The nonfusellar periderm of the prosicula is pitted by many depressions similar to pits in the cortical tissue of graptolites.

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3D domain swapping – implications for conformational disorders and ways of control

80%

Jaskolski M.

BioTechnologia. Journal of Biotechnology Computational Biology and Bionanotechnology

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2011

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tom 92

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nr 1

Ograniczanie wyników

1 Acta Neurobiologiae Experimentalis

1 Acta Palaeontologica Polonica

1 BioTechnologia. Journal of Biotechnology Computational Biology and Bionanotechnology

1 Jankowska E.

1 Jaskolski M.

1 Kulicki C.

1 Mierzejewski P.

1 Sosnowska M.

1 2013

1 2011

1 2003

Inhibition of serum amyloid A protein amyloid formation

Cortical fibrils and secondary deposits in periderm of the hemichordate Rhabdopleura [Graptolithoidea]

3D domain swapping – implications for conformational disorders and ways of control