Transcriprome analysis reveals possible mechanisms of neuroprotective effect of Torin-2 in Drosophila melanogaster

Currently, there are no effective enough drugs for the treatment of most neurodegenerative disorders in the world. At the same time, the problem of age-associated diseases, including neurodegenerative pathologies, is becoming increasingly urgent. Torin-2, a synthetic compound, appeared as a highly selective inhibitor of both mTORC1 and 2 (target of rapamycin) complexes as an alternative to the well-known immunosuppressor, geroprotector and potential anti-cancer natural compound Rapamycin. Rapamycin and his analogs (rapalogs) were also previously put forward as an effective neuroprotective agent. The similarity of target proteins and mechanisms of action of these compounds suggest that Torin-2 may possess similar neuroprotective properties. At the same time, Torin-2 is effective at hundreds of times lower concentrations and prevents negative side effects of rapamycin. The purpose of this study was to detect changes in gene expression in the brain of the model object D.melanogaster caused by chronic intermittent administration of Torin-2. We found that Torin-2 activated of genes gene expression encoding for heat shock proteins, regulation of synaptic plasticity, neurotransmitter transmission, and had positive effects on pathways involved in learning and memory. Using western blotting analysis, we determined that the downstream effect of Torin-2 also include the increase of the active, phosphorylated form of components MAPK pathway in the brain, which plays a significant role in memory formation. This study provides insight into the role of Torin-2 in neuroprotection and suggests that Torin-2 may be a potential candidate for the prevention and treatment of neurodegenerative diseases. The data we obtained represent an extensive field for further research