Themed collection Amyloids and Protein Aggregation

Sara Linse and Tuomas Knowles introduce the Chemical Science themed collection on the topic of amyloids and protein aggregation.

The current amyloid hypothesis does not capture the full complexity of Aβ aggregation. Here we lay out a supersaturation framework to better understand the molecular mechanism of Alzheimer’s disease and to develop more effective treatment strategies.

The molecular mechanisms of amyloid formation have been studied extensively in test tube reactions. This perspective article addresses the question to what extent these mechanisms apply to the complex situation in living cells and organisms.

The thermodynamics of amyloid formation has largely been neglected compared to kinetic studies. In this review, the current state of the experimental exploration of amyloid thermodynamics is presented and important open questions are highlighted.

Functional bacterial amyloids forming biofilms have unique structural characteristics while still being similar to pathological ones. Through many identified interaction partners, they emerge as complex and essential components of biofilms.

Extracellular accumulation of β amyloid peptides of 40 (Aβ₄₀) and 42 residues (Aβ₄₂) has been considered as one of the hallmarks in the pathology of Alzheimer's disease.

The pathology of Alzheimer's disease is connected to the aggregation of β-amyloid (Aβ) peptide, which in vivo exists as a number of length-variants. This study identifies the Aβ37/38/40 ratio that is maximally inhibitory to Aβ₄₂ aggregation.

A computational maturation method enables the generation of an antibody variant with over 200-fold increased potency against the primary nucleation process in Aβ42 aggregation.

A little leak will sink a great ship! We prepared a series of multi-color protein aggregation sensors and developed a dual-color thermal shift assay to simultaneously and quantitatively report on protein co-aggregation of two different proteins.

Cryo-electron tomography 3D imaging of amyloid-β oligomers carpeting the surface of lipid bilayers in near native conditions.

Biomolecular condensates sequester an aggregation-prone peptide and prevent its aggregation, showing that heterotypic interactions within the condensates can prevent the formation of amyloid fibrils, despite the local increase in concentration.

The extent of protein hydration modulates the free energy barrier of both heterogeneous and homogeneous α-synuclein nucleation, leading to the formation of distinct amyloid polymorphs depending on the water activity of the protein microenvironment.

Amyloid fibril elongation of α-synuclein can be described with the Michaelis–Menten model, where α-synuclein monomer plays a dual role by serving as growth substrate as well as supporting the competitive inhibitor CC48 in blocking fibril ends.

A remarkable inhibition effect and chiral discrimination are observed when the amyloid peptide aggregates on chiral phospholipid surfaces.

A general non-binary definition for on- and off-pathway intermediates is developed, enabling comparison of amyloid oligomers' contributions to fibril formation.

A small molecule fluorescence probe ICTAD-1 was rationally designed for differentiating Aβ40 and Aβ42 in solutions and in Aβ plaques.

A comprehensive analysis on the impact of sedimentation, microgravity hydrodynamic mixing and air–water interface on α-synuclein aggregation kinetics.

We have employed glass nanopore as a single molecule technique for direct sensing amyloidosis process of Aβ1–42 peptide, which of great significance in Alzheimer's disease.

Atomic resolution map of the soluble amyloid beta assembly (Aβ_n) “toxic surfaces” that facilitate the early pathogenic events in Alzheimer's disease (AD).

Modular genetic design of functional amyloids represents new opportunities for creating multifunctional molecular materials with tailored structures and performance.

Simultaneous analysis of oligomer and fibril assembly kinetics reveals inhibitory effects of metastable oligomers on amyloid fibril formation.

C-terminal truncations shift the pH range at which α-synuclein secondary nucleation occurs from acidic to neutral values.

Understanding the molecular determinants of fibrillogenesis by studying the aggregation propensities of high homologous proteins with different folding pathways.

Aβ₄₀ and Aβ₄₂ co-aggregate and form oligomers with mixed β-sheets as revealed by isotope-edited infrared spectroscopy.

A general reaction network for filamentous self-assembly unifies mechanistic descriptions and links the overall scaling behaviour to the underlying rate-determining steps.

Co-assembly into hetero-oligomers controls the lag time of amylin assembly by a mechanism reminiscent of prions.

The aggregation of Aβ42, linked to Alzheimer's disease, can be altered significantly by variations of the ionic strength of the solution, providing a means to relate the differences in aggregation mechanism of other Ab variants to changes in electrostatic interactions.

Reaction network starting from monomer mixtures of Aβ40 and Aβ42. Interaction at the level of primary nucleation only accelerates Aβ40 fibril formation. Separate fibrils form as secondary nucleation and elongation are highly specific.