Mitochondrial dysfunction is implicated in Parkinson’s Disease (PD), but a detailed understanding of the cause and effect in αSyn toxicity is lacking. Through the provision of quantitative and systematic characterization of mitochondrial dysfunction, PD-MitoQUANT will provide an unprecedented understanding of the role of mitochondrial dysfunction in PD, identify and validate novel disease biomarkers, and propose innovative therapeutic targets that can be further progressed by the EFPIA partners. The consortium leverages multi-disciplinary expertise in the fields of αSyn biochemistry, iPSC-derived PD models, mitochondrial function and structural analysis, proteotoxicity, ER stress and UPR signaling, systems biology of mitochondrial function, and in vivo animal models. A key focus will be quantitative description and integrated analysis of mitochondrial function and its relation to proteotoxicity; representing a key panel of consortium partners Prehn [RCSI], Abramov [UCL], Corti [ICM] and Koopmann [RUMC] who also have assembled long-standing expertise in primary neuron culture, iPSC-derived neurons, PD in vivo models, proteostasis and ageing studies.
These investigations will be supported by expert teams in iPSC-derived in vitro PD models and in vivo PD models from the academic partners (Hunot [ICM], Melki [CNRS], Di Monte [DZNE], Broccoli [CNR], SME [Mimetas] and EFPIA partners [Teva], [Lundbeck] and [UCB]. Through integrated in-vitro, in-silico and in-vivo approaches, and supported computationally by SME [GENEXPLAIN], PD-MitoQUANT will perform thorough and unprecedented investigations of mitochondrial dysfunction.
Finally, the consortium will initiate a European research platform of excellence investigating mitochondrial dysfunction in PD continuing beyond the project, further supported by [PUK]’s PD human tissue biobank. This will provide long-term and sustainable progress in the understanding of mitochondrial dysfunction in PD and towards clinical application.
It is geneXplain’s role in this consortium to apply its proprietary methodology of computational upstream analysis and master regulator search to the data generated by the project partners.