Processus Degeneratifs du Neurone et de ses Reseaux
Responsables Etienne JACOTOT et Bernard BRUGG
Neurodegenerative diseases such as Alzheimer Disease and Parkinson are characterized by slow and progressive neuronal dysfunctions, like synaptic and axonal degeneration that occur over a long time period. Recent studies showed that pathological hallmarks progress spatially and temporally in the brains of affected patients along neuronal pathways. Axonal and synaptic degeneration are key events in peripheral neuropathies and brain neurodegenerative syndromes. However, the cellular and molecular mechanisms involved in these processes are poorly understood. Our project aims to decipher, at the molecular level, how a degenerative process is able to progress spatially in a neuron and how it is capable of progressing trans-synaptically to the postsynaptic neuron. Current experimental models are poorly adapted to efficiently and reliably study the detailed molecular/cellular phenomena. Our project includes two fundamental biological research aims where we plan to exploit our expertise in microfluidic technology to study compartmentalization of molecular mechanisms involved in neuronal degeneration, comprising the propagation of apoptotic signals/effectors and the role of mitochondrial dynamics in this process. The second aim is focused on synaptic and trans-synaptic degeneration, where we will study the role of extra synaptic excitotoxicity and dispersion of aggregated proteins. The last aim that we will keep developing in collaboration with physics laboratories comprises the development of an industry-oriented platform for cultured neuronal networks and biological assays for efficient in vitro screening and validating potential drug candidates. This project brings to the Unit the technology to dissect the evolution of pathological processes in different subcellular compartments.

B2A UMR 8256 @Février 2014