Serine phosphorylation mimics of Aβ form distinct, non-cross-seeding fibril morphs.

The self-assembly of amyloid-β peptide (Aβ) into fibrils and oligomers is linked to Alzheimer's disease (AD). Fibrillar aggregates in AD patient's brains contain several post-translational modifications, including phosphorylation at positions 8 and 26. These play a key role in modifying the aggregation propensity of Aβ, yet how they affect the mechanism of aggregation is only poorly understood.

Insights into the Hierarchical Assembly of a Chemically Diverse Peptide Hydrogel Derived from Human Semenogelin I.

A peptide corresponding to a 13-residue segment of the human protein semenogelin I has been shown to generate a hydrogel consisting of amyloid-like fibrils. The relative chemical diversity (compared to synthetic sequences) with 11 distinct amino acids makes this peptide (P0) an ideal candidate for investigating the role of individual residues in gelation. Herein, the terminal residues have been sequentially removed to furnish a series of truncated peptides, P1-P10, ranging from 12 to 3 residues in length.

pH-Responsive Capsules with a Fibril Scaffold Shell Assembled from an Amyloidogenic Peptide.

Peptides and proteins have evolved to self-assemble into supramolecular entities through a set of non-covalent interactions. Such structures and materials provide the functional basis of life. Crucially, biomolecular assembly processes can be highly sensitive to and modulated by environmental conditions, including temperature, light, ionic strength and pH, providing the inspiration for the development of new classes of responsive functional materials based on peptide building blocks.

The role of fibril structure and surface hydrophobicity in secondary nucleation of amyloid fibrils.

Crystals, nanoparticles, and fibrils catalyze the generation of new aggregates on their surface from the same type of monomeric building blocks as the parent assemblies. This secondary nucleation process can be many orders of magnitude faster than primary nucleation. In the case of amyloid fibrils associated with Alzheimer's disease, this process leads to the multiplication and propagation of aggregates, whereby short-lived oligomeric intermediates cause neurotoxicity.

Autocatalytic amplification of Alzheimer-associated Aβ42 peptide aggregation in human cerebrospinal fluid.

Alzheimer's disease is linked to amyloid β (Aβ) peptide aggregation in the brain, and a detailed understanding of the molecular mechanism of Aβ aggregation may lead to improved diagnostics and therapeutics. While previous studies have been performed in pure buffer, we approach the mechanism in vivo using cerebrospinal fluid (CSF). We investigated the aggregation mechanism of Aβ42 in human CSF through kinetic experiments at several Aβ42 monomer concentrations (0.