Abstract
Alzheimer’s disease (AD) is a complex neurodegenerative disorder of impaired proteostasis. An in-depth understanding of protein complexes, their components, interaction and post translational modification (PTM) is crucial for gaining insight of AD pathology. This study aims to identify novel disease associated protein interactions and their potential phosphorylation and glycosylation (O-GlcNAc) involved in the progression of AD, to help unravel the underlying disease mechanisms. Thirteen protein complexes were obtained on Blue native PAGE (BN-PAGE) from human brain prefrontal cortex of AD and age matched controls. Complex VII (305Kda) entailing pronounced alteration was further resolved into its components on SDS-PAGE and identified by mass spectrometric analysis. The differentially expressed proteins were mapped to existing biological networks and analyzed for potential phosphorylation and O-GlcNAc. Glyceraldehyde-3- PO4 dehydrogenase (GAPDH), actin cytoplasmic (ACTB), microtubule associated protein 1B (MAP1B), myelin proteolipid protein (PLP1), acyl amino acid releasing enzyme (APEH) were found to be differentially expressed among AD and control brain. Further, network analysis reveals a strong interaction between metabolic proteins (GAPDH, APEH) and their cytoskeletal counterparts (MAP1B, ACTB, PLP1). The annotated network and pathways associated with altered proteins along with their PTM warrants further research to study their actual contribution in AD pathology.
