Amplification of Amyloid Protein-induced Aggregation of the Eukaryotic
Ribosome

Sehnaz      Ferdosh; Senjuti      Banerjee; Chandana      Barat

doi:10.2174/0929866529666220905112156

Abstract

Background: Alzheimer’s disease (AD) is characterized by the aggregation of Tau protein and Amyloid-β peptides (Aβ 1-40 and Aβ 1-42). A loss of ribosomal population is also observed in the neurons in affected regions of AD. Our studies demonstrated that in vitro aggregation of amyloid forming proteins, Aβ peptides and Tau protein variants (AFPs), in the vicinity of yeast 80S ribosome can induce co-aggregation of ribosomal components.

Objective: In this study, the ability of minute quantities of AFP-ribosome co-aggregates to seed the aggregation of a large excess of untreated 80S ribosomes was explored.

Methods: The AFPs were purified using ion-exchange chromatography. Seeded aggregation of ribosomes in the presence of minute quantities of ribosome-protein co-aggregates or ribosomal components was studied using agarose gel electrophoretic and SDS-PAGE analysis of the pellets and Sucrose Density Gradient centrifugation of the supernatant obtained after centrifugation of the aggregation reaction mixture.

Results: Our studies, therefore, demonstrate that minute quantities of AFP-80S co-aggregate have significant seeding potential and could lead to aggregation of a large excess of fresh 80S ribosomes and this seeding ability is sustained over multiple cycles of ribosome aggregation. The aggregation propensity of ribosomal components alone could contribute towards the seeding of ribosome aggregation.

Conclusion: The ability of minute quantities of AFP-80S co-aggregates to seed the aggregation of a large excess of fresh 80S ribosomes would result in the loss of global ribosomal population in Alzheimer’s disease afflicted neurons. Hence, subject to further validation by in vivo studies, our in vitro studies indicate a significant mode of toxicity of amyloid aggregates that might be important in Alzheimer’s disease pathology.

Keywords: Amyloid-β, Tau protein, Ribosome, Aggregation, Seeding, Alzheimer’s disease, Ribosomal RNA (rRNA), Ribosomal protein

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Amplification of Amyloid Protein-induced Aggregation of the Eukaryotic Ribosome

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