Moving from mechanism to therapy requires experimental systems where compounds, genetic interventions and disease models can be tested side by side. In this theme, DHD and FGU work together to offer in vivo Drosophila assays and advanced in vitro neuronal/iPSC models as complementary platforms for neuroprotective discovery, compound prioritization and mechanistic drug repurposing.
On the discovery side, we have identified the pyrazolopyridine alkaloid S88 as a small molecule that mitigates neuronal ER stress and age-related functional decline, restoring ER–mitochondria homeostasis without blocking physiological stress signaling. On the repurposing side, we have demonstrated that fingolimod, approved for multiple sclerosis, can ameliorate TDP-43-driven ALS phenotypes in Drosophila, improving motor performance and reducing neurodegeneration. Building on our expertise in YEATS-domain biology, we are also evaluating selective YEATS inhibitors, originally developed for leukemia, as context-dependent modulators of neuronal stress and metabolism.
Through this theme, we collaborate with academic and clinical partners to test natural compounds, approved drugs and targeted probes in robust neurological models, aiming to identify the conditions under which specific interventions truly benefit the aging or diseased brain.
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