Comparisons with Amyloid-β Reveal an Aspartate Residue That Stabilizes Fibrils of the Aortic Amyloid Peptide Medin

Comparisons with Amyloid-β Reveal an Aspartate Residue That Stabilizes Fibrils of the Aortic Amyloid Peptide Medin*

Aortic medial amyloid (AMA) is the most common localized human amyloid, occurring in virtually all of the Caucasian population over the age of 50. The main protein component of AMA, medin, readily assembles into amyloid-like fibrils in vitro. Despite the prevalence of AMA, little is known about the self-assembly mechanism of medin or the molecular architecture of the fibrils. The amino acid seq...

Studies on medin amyloid formation and involvement in aortic pathology

Immunoprecipitation of Amyloid Fibrils by the Use of an Antibody that Recognizes a Generic Epitope Common to Amyloid Fibrils

Amyloid fibrils are associated with many maladies, including Alzheimer's disease (AD). The isolation of amyloids from natural materials is very challenging because the extreme structural stability of amyloid fibrils makes it difficult to apply conventional protein science protocols to their purification. A protocol to isolate and detect amyloids is desired for the diagnosis of amyloid diseases ...

Brazilin inhibits amyloid β-protein fibrillogenesis, remodels amyloid fibrils and reduces amyloid cytotoxicity

Soluble amyloid β-protein (Aβ) oligomers, the main neurotoxic species, are predominantly formed from monomers through a fibril-catalyzed secondary nucleation. Herein, we virtually screened an in-house library of natural compounds and discovered brazilin as a dual functional compound in both Aβ42 fibrillogenesis inhibition and mature fibril remodeling, leading to significant reduction in Aβ42 cy...

Nucleation of amyloid fibrils.

We consider nucleation of amyloid fibrils in the case when the process occurs by the mechanism of direct polymerization of practically fully extended protein segments, i.e., beta-strands, into beta-sheets. Applying the classical nucleation theory, we derive a general expression for the work to form a nanosized amyloid fibril (protofilament) constituted of successively layered beta-sheets. Analy...