amyloid-beta-peptides has been researched along with Amyloid-Neuropathies--Familial* in 2 studies
2 other study(ies) available for amyloid-beta-peptides and Amyloid-Neuropathies--Familial
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Evidence for novel beta-sheet structures in Iowa mutant beta-amyloid fibrils.
Asp23-to-Asn mutation within the coding sequence of beta-amyloid, called the Iowa mutation, is associated with early onset, familial Alzheimer's disease and cerebral amyloid angiopathy, in which patients develop neuritic plaques and massive vascular deposition predominantly of the mutant peptide. We examined the mutant peptide, D23N-Abeta40, by electron microscopy, X-ray diffraction, and solid-state NMR spectroscopy. D23N-Abeta40 forms fibrils considerably faster than the wild-type peptide (k = 3.77 x 10(-3) min(-1) and 1.07 x 10(-4) min(-1) for D23N-Abeta40 and the wild-type peptide WT-Abeta40, respectively) and without a lag phase. Electron microscopy shows that D23N-Abeta40 forms fibrils with multiple morphologies. X-ray fiber diffraction shows a cross-beta pattern, with a sharp reflection at 4.7 A and a broad reflection at 9.4 A, which is notably smaller than the value for WT-Abeta40 fibrils (10.4 A). Solid-state NMR measurements indicate molecular level polymorphism of the fibrils, with only a minority of D23N-Abeta40 fibrils containing the in-register, parallel beta-sheet structure commonly found in WT-Abeta40 fibrils and most other amyloid fibrils. Antiparallel beta-sheet structures in the majority of fibrils are indicated by measurements of intermolecular distances through (13)C-(13)C and (15)N-(13)C dipole-dipole couplings. An intriguing possibility exists that there is a relationship between the aberrant structure of D23N-Abeta40 fibrils and the unusual vasculotropic clinical picture in these patients. Topics: Amyloid; Amyloid beta-Peptides; Amyloid Neuropathies, Familial; Aspartic Acid; Benzothiazoles; Glutamic Acid; Humans; Kinetics; Leucine; Lysine; Microscopy, Electron, Transmission; Models, Molecular; Mutation, Missense; Nuclear Magnetic Resonance, Biomolecular; Peptide Fragments; Phenylalanine; Protein Structure, Secondary; Spectrometry, Fluorescence; Thiazoles; X-Ray Diffraction | 2009 |
Only amyloidogenic intermediates of transthyretin induce apoptosis.
In diseases like Alzheimer's disease and familial amyloidotic polyneuropathy (FAP) amyloid deposits co-localize with areas of neurodegeneration. FAP is associated with mutations of the plasma protein transthyretin (TTR). We can here show an apoptotic effect of amyloidogenic mutants of TTR on a human neuroblastoma cell line. Toxicity could be blocked by catalase indicating a free oxygen radical dependent mechanism. The toxic effect was dependent on the state of aggregation and unexpectedly mature fibrils from FAP-patients who failed to exert an apoptotic response. Morphological studies revealed a correlation between toxicity and the presence of immature amyloid. Thus, we can show that toxicity is associated with early stages of fibril formation and propose that mature full-length fibrils represent an inert end stage, which might serve as a rescue mechanism. Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid Neuropathies, Familial; Apoptosis; Catalase; Cytoprotection; Dose-Response Relationship, Drug; Humans; In Situ Nick-End Labeling; Mutagenesis, Site-Directed; Neuroblastoma; Peptide Fragments; Prealbumin; Protein Binding; Structure-Activity Relationship; Tumor Cells, Cultured | 2002 |