Evaluating the metabolic consequences of small molecule treatment in a Drosophila model for Parkinson's Disease

Parkinson's Disease (PD) is the second most common neurodegenerative disorder, characterized by a wide range of motor and non-motor symptoms. Different studies have suggested that mitochondrial dysfunction, in particular a systemic deficiency in the Complex I activity of the mitochondrial electron transport chain (ETC) may be an early and determinant feature of PD pathogenesis. However, the precise mechanisms linking bioenergetic perturbations to PD onset and progression remain poorly understood. In this study, we propose a novel therapeutic approach utilizing a small molecule that may be able to bypass the dysfunctional components of the ETC and alleviate metabolic impairments. To investigate this, we administered a specific small molecule to a well-established Drosophila model of PD and assessed its effects on major metabolic pathways and PD-related hallmarks. Our findings reveal a significant improvement in neurolocomotor abilities, accompanied by a considerable extension of lifespan. Moreover, we observed potential effects on ATP levels, NAD/NADH ratio, and mitochondrial respiration. These findings highlight the potential metabolic targets and mechanisms involved in PD pathogenesis and provide insights into new possible therapeutic interventions. Further investigation is warranted to elucidate the precise molecular mechanisms underlying the observed metabolic changes and their therapeutic implications.