Grant: Project Grant

More than a century ago, the neurologist Friedrich Lewy described for the first time, in the brain of patients suffering from Parkinson's disease (PD), the presence of abnormal protein inclusions, called Lewy bodies (LBs). These inclusions have been suggested to play a deleterious role in the brain and to induce neuronal loss. However, the exact mechanisms by which these inclusions precipitate the cell death and PD progression remain unknown. In our laboratory, we took advantage of recent technologies, allowing the manipulation of protein clustering under light (optogenetic), to create a new cellular and animal model of PD based on the formation of intra-neuronal inclusions mimicking PD-derived authentic LBs. Using this unique model, we will seek to address the question on how LBs disrupt the neuronal functions leading to neuronal degeneration in the brain and progression of PD. The expected results will help us identify new pharmacological targets for the development of effective therapies for PD and related disorders.