Sequential Molecular Interactions Shape Aβ42 Aggregation, Propagation, and Toxicity
Protein aggregation is a context-dependent process in which the molecular environment can influence the properties of the resulting assemblies. In biological systems, these interactions can occur sequentially, as aggregates formed in one cellular or tissue context may encounter different molecular partners and act as seeds in subsequent aggregation events. Here, we used sequential seeding as a…
Protein aggregation, a process that depends on the surrounding environment, can occur in a sequential manner. In biological systems, aggregates formed in one context may encounter different molecular partners and act as seeds in subsequent aggregation events. Researchers utilized sequential seeding as a controlled experimental model to examine how prion-like sequences from the gut microbiome influence amyloid-{beta} aggregation across successive cycles.
By employing kinetic, biophysical, conformational, and toxicity analyses, they discovered that initial interactions with external peptides alter the characteristics of first-generation A{beta}40- and A{beta}42-derived seeds, leading to propagated A{beta}42 assemblies with unique molecular and functional properties. These findings support the concept of an Interaction History model, where exogenous sequences influence the formation of aggregate populations whose properties and propagation depend on the molecular contexts encountered during earlier aggregation events.
The study concludes that A{beta} aggregation behaves as a history-dependent process, and single-step assays might not capture the diversity of aggregates that arise across successive aggregation cycles.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
