Identification of differentially expressed novel tau associated proteins in transgenic AD model of Drosophila - a proteomic and in silico Approach

Alzheimers disease (AD) is a memory related neurodegenerative disorder mainly associated with older adults. In this study, transgenic Drosophila AD model has been employed to investigate the tau associated proteome. Tau expression was specifically induced in the eye tissues and diseased fly heads were considered for proteomic studies with appropriate controls. We have identified 6 novel proteins from tau induced AD group by 2D and PD Quest analyses and further characterized them by in-vivo and in-silico approaches. The novel Tau interactors, [Obp44a Isoform A, Pglym Isoform A, IP15846p (Adh variant), RE45450p (mRpL2), Retinin, and Glob1 Isoform B], identified by MALDI-TOF/MS were validated through q-RT-PCR. The altered metabolic, behavioral and mitochondrial dynamics associated with Tau over expressing AD flies could be due to the altered expression of Odorant binding protein 44a (Obp44a) and mitochondrial ribosomal protein L2 (mRpL2), respectively. Further, we have showed for the first time the newly identified protein interaction with tau and other regulatory proteins through protein-protein docking, biocomputational classification and evolutionary relationship using in silico studies. Moreover, the study highlights the plausible role of these novel proteins in pathophysiology of phospho-tau induced AD flies and further help unraveling molecular pathways implicated in tauopathies.