Amyloid protein-induced sequestration of the eukaryotic ribosome: effect of stoichiometry and polyphenolic inhibitors

Alzheimer's disease (AD) is characterized by the appearance of neurofibrillary tangles comprising of the Tau protein and aggregation of amyloid-beta peptides (A beta 1-40 and A beta 1-42). A concomitant loss of the ribosomal population is also observed in AD-affected neurons. Our studies demonstrate that, similarly to Tau protein aggregation, in vitro aggregation of A beta peptides in the vicinity of the yeast 80S ribosome can induce co-aggregation of ribosomal components. The RNA-stimulated aggregation of A beta peptides and the Tau-K18 variant is dependent on the RNA:protein stoichiometric ratio. A similar effect of stoichiometry is also observed on the ribosome-protein co-aggregation process. Polyphenolic inhibitors of amyloid aggregation, such as rosmarinic acid and myricetin, inhibit RNA-stimulated A beta and Tau-K18 aggregation and can mitigate the co-aggregation of ribosomal components.

Automated summary

Alzheimer's disease is a neurodegenerative disease characterized by the aggregation of Tau protein and amyloid-beta peptides. Research has shown that the in vitro aggregation of A beta peptides in the vicinity of the ribosome can induce the co-aggregation of ribosomal components. The stoichiometry of RNA:protein and polyphenolic inhibitors also play a role in this process.