Unveiling Ribosomal Dysfunction and Impaired Signaling Pathways in the Cortical Region of FAD5x Mice

Elevated expression of RPL11, RPL6, and other large ribosomal subunit proteins was observed, consistent with impaired protein synthesis. This dysregulation may contribute to neurodegenerative processes in AD. Among the large subunit ribosomal proteins, RPL29 were downregulated at the gene expression level in AD, although its protein expression revealed a statistically insignificant rise.

Comparison between the transcriptome and proteome demonstrated evidence of impaired translation, suggesting failed translational control. Lipidomic analyses revealed alterations in the levels of phospholipids, sphingolipids and lipid mediators in AD that is closely linked to the alterations in the neuroinflammatory pathways at the transcriptomic and proteomics levels. Multi-omics integration demonstrates that ribosomal dysregulation, oxidative stress, and protein homeostasis are affected, leading to neuronal damage in AD.

According to this study, ribosomal malfunction plays a significant role in the pathophysiology of AD and serve as a potential target for therapeutic interventions.