In silico characterization of the protein Aβ175 from circular RNA CircAβ-a and its involvement in the pathogenesis of Alzheimer’s disease (AD)

Circular RNAs are specialized single-stranded molecules having covalently closed termini. They were once thought to be mere transcriptional artefacts. However, they have now been identified as significant players in tumorigenesis, neurodegeneration and other diseases. Though generally classified as non-coding, certain circular RNAs demonstrate the ability to encode proteins, reshaping our understanding of their biological roles. CircAβ-a, a circRNA that contains the amyloid beta (Aβ)-coding region of the APP gene, acts as an alternative source of Aβ peptides. The discovery of circAβ-a suggests that Aβ peptides can be generated through a non-canonical translation mechanism, independent of APP processing and that Aβ peptides are the key contributors to Alzheimer’s Disease pathogenesis. CircAβ-a is efficiently translated into Aβ175, which is further processed into Aβ peptides. Inhibiting circAβ-a translation or modifying its expression might help in reducing Aβ accumulation in brain. To develop effective inhibitors for Aβ peptides, it is crucial to understand its structural characteristics, functional properties and interaction patterns. This study focuses on characterizing the Aβ175 protein by predicting its structural features to explore its potential as an alternative biomarker, which can be verified through wet-lab experiments, for the treatment of Alzheimer’s Disease.