Nesfatin-1 ameliorates pathological abnormalities in Drosophila hTau model of Alzheimer's disease

In human Alzheimer's disease (AD), the aggregation of tau protein is considered a significant hallmark, along with amyloid-beta. The formation of neurofibrillary tangles due to aberrant phosphorylation of tau disrupts microtubule stability, leading to neuronal toxicity, dysfunction, and subsequent cell death. Nesfatin-1 is a neuropeptide primarily known for regulating appetite and energy homeostasis. However, the function of Nesfatin-1 in a neuroprotective role has not been investigated. In this study, we aimed to elucidate the effect of Nesfatin-1 on tau pathology using the Drosophila model system. Our findings demonstrate that Nesfatin-1 effectively mitigates the pathological phenotypes observed in Drosophila human Tau overexpression models. Nesfatin-1 overexpression rescued the neurodegenerative phenotypes in the adult fly's eye and bristle. Additionally, Nesfatin-1 improved locomotive behavior, neuromuscular junction formation, and lifespan in the hTau AD model. Moreover, Nesfatin-1 controls tauopathy by reducing the protein level of hTau. Overall, this research highlights the potential therapeutic applications of Nesfatin-1 in ameliorating the pathological features associated with Alzheimer's disease. •In Drosophila hTau model of AD, Nesfatin-1 rescued the neurodegenerative phenotypes observed in the eye and bristle.•Nesfatin-1 improved the locomotive behavior and neuromuscular junction formation in the hTau AD model.•Nesfatin-1 rescued aging phenotypes including lifespan and ubiquitination in brains.•Nesfatin-1 controls tauopathy by reducing the protein level of hTau.