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- Rahman, Mashuqur, 1984-, et al.
(författare)
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Enhanced detection of ATTR amyloid using a nanofibril-based assay
- 2021
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Ingår i: Amyloid. - : Taylor and Francis Ltd.. - 1350-6129 .- 1744-2818. ; 28:3, s. 158-167
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Tidskriftsartikel (refereegranskat)abstract
- More than 30 proteins and peptides have been found to form amyloid fibrils in human diseases. Fibrils formed by transthyretin (TTR) are associated with ATTR amyloidosis, affecting many vital organs, including the heart and peripheral nervous system. Congo red staining is the gold standard method for detection of amyloid deposits in tissue. However, Congo red staining and amyloid typing methods such as immunofluorescence labelling are limited to relatively large deposits. Detection of small ATTR deposits present at an early stage of the disease could enable timely treatment and prevent severe tissue damage. In this study, we developed an enhanced ATTR amyloid detection method that uses functionalised protein nanofibrils. Using this method, we achieved sensitive detection of monomeric TTR in a microplate immunoassay and immunofluorescence labelling of ex vivo tissue from two patients containing ATTR aggregates. The system's utility was confirmed on sections from a patient with AA amyloidosis and liver sections from inflamed mouse. These results suggest that the detection system constitutes important new technology for highly sensitive detection of microscopic amounts of ATTR amyloid deposited in tissue.
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| 2. |
- Rahman, M. Mahafuzur, et al.
(författare)
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Extracellular protein components of amyloid plaques and their roles in Alzheimer's disease pathology
- 2021
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Ingår i: Molecular Neurodegeneration. - : Springer Nature. - 1750-1326. ; 16:1
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Forskningsöversikt (refereegranskat)abstract
- Alzheimer's disease (AD) is pathologically defined by the presence of fibrillar amyloid beta (A beta) peptide in extracellular senile plaques and tau filaments in intracellular neurofibrillary tangles. Extensive research has focused on understanding the assembly mechanisms and neurotoxic effects of A beta during the last decades but still we only have a brief understanding of the disease associated biological processes. This review highlights the many other constituents that, beside A beta, are accumulated in the plaques, with the focus on extracellular proteins. All living organisms rely on a delicate network of protein functionality. Deposition of significant amounts of certain proteins in insoluble inclusions will unquestionably lead to disturbances in the network, which may contribute to AD and copathology. This paper provide a comprehensive overview of extracellular proteins that have been shown to interact with A beta and a discussion of their potential roles in AD pathology. Methods that can expand the knowledge about how the proteins are incorporated in plaques are described. Top-down methods to analyze post-mortem tissue and bottom-up approaches with the potential to provide molecular insights on the organization of plaque-like particles are compared. Finally, a network analysis of A beta-interacting partners with enriched functional and structural key words is presented.
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