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From Huntington Disease to Axonal Transport, Neurotrophin Signaling and Energy Metabolism| title | From Huntington Disease to Axonal Transport, Neurotrophin Signaling and Energy Metabolism |
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| start_date | 2024/01/18 |
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| schedule | 11h30 |
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| online | no |
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| location_info | / |
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| summary | Huntington’s disease (HD) is caused by the abnormal polyglutamine expansion in the N-ter part of huntingtin (HTT), a large protein of 350kDa. Over the past years, we proposed that HTT acts a scaffold for the molecular motors and through this function, regulates the efficiency and directionality of vesicular transport along microtubules in neurons. In particular, HTT controls the microtubule-based fast axonal transport (FAT) of neurotrophic factors such as BDNF. HTT function in transport is modulated by direct phosphorylation/dephosphorylation via specific signaling pathways. Importantly, polyQ expansion in HTT alters this function, leading to a decrease in neurotrophic support and death of striatal neurons.
In addition to the role of HTT in scaffolding the molecular motors both in cortical and striatal neurons, we found that HTT scaffolds the whole glycolytic machinery on vesicles and supply constant energy for the transport of vesicles over long distances in axons.
We will discuss how these machineries are altered in disease situation using new approaches that allow the study of healthy and defective networks in vitro through the development of microfluidic systems compatible with high-resolution videomicroscopy and the use of biosensors to reconstitute and identify each component of the corticostriatal network. Using these approaches, we recently identified compounds of therapeutic interest as well as new cellular mechanisms by which signaling endosomes find their way to the nucleus by having an on-board navigational system. We will discuss how endosomes start their journey to the nucleus by activating a specific fueling system present on vesicles and whether such mechanisms are impaired in HD. |
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| responsibles | Perrais, Thoumine |
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Workflow history| from state (1) | to state | comment | date |
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| submitted | published | | 2023/12/20 12:33 UTC |
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