Impact of Enteric Tau On the Development and Structural Integrity of Sensory and Non-Sensory Organs in Drosophila melanogaster

Abstract

Tau (Tubulin Associated Unit) is a widely recognized microtubule-associated protein that play crucial role in Alzheimer's diseases (AD). Under pathological conditions, hyperphosphorylated Tau detaches from microtubules, contributing to neurodegeneration through inflammation, neuronal dysfunction, and cell death. Aggregated Tau is present in the brain and gut of AD patients. Although, the role of Tau in the brain has been extensively investigated; its significance within the gut remains comparatively unexplored. Similarly, less information is available for the toxic effect of monomeric and oligomeric Tau. In this study, we have investigated the effect of monomeric, oligomeric, and aggregated Tau within the gut of Drosophila melanogaster. To evaluate the toxic effect of three different forms of Tau different cytotoxic and genotoxic parameters were taken into account. Third-instar larvae were fed to 10 μM concentrations of different Tau protein and guts were analyzed using Dichloro-dihydro-fluorescein diacetate, DAPI and TUNEL assay. Reactive oxygen species levels were measured from hemolymph extracts using the NBT assay. Developmental defects after exposure of Tau proteins were analyzed across larva, pupa, and adult stages. Histological examinations revealed cytoskeletal alterations within the sensory and non-sensory organs of adult flies. These results reveal Tau’s effects beyond the nervous system, emphasizing the need to study its role in peripheral tissues to understand the AD pathology.