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Les mécanismes moléculaires de la dégénérescence axonale dans un contexte de type Dying back pattern

Abstract : In Alzheimer's disease, neurons die through a process of programmed cell death, called apoptosis. In vivo studies have shown that this stage of somatic destruction, late, is preceded by phenomena of early synaptic dysfunction and axonal degeneration. However, in the absence of appropriate tools, their methods and their molecular mechanisms remain poorly understood. We propose to tackle this issue using a new system of primary culture of neurons called "microfluidic" for effective compartmentalization of axons and somas of neurons from the central nervous system. With this tool we show that a stress applied only at the cell body is sufficient to induce axonal degeneration. It therefore seems that a signal has spread degeneration in the axon from the soma. From a molecular point of view, the map kinase JNK involved in the early stages of apoptosis is by the first signal observed in the axon, controlling the fission of mitochondria and caspase activation, which are the molecular effectors of the execution phase of apoptosis. Furthermore, we demonstrated that the NAD +, a key element in the bioenergetics of the neuron, was also involved. Thus our results suggest that NAD + and apoptosis can all become involved in the axon. In conclusion, this work fits into understanding the mechanisms of axonal degeneration observed in neurodegenerative diseases such as Alzheimer's disease
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Submitted on : Wednesday, June 12, 2013 - 11:51:49 AM
Last modification on : Sunday, June 26, 2022 - 9:39:36 AM
Long-term archiving on: : Friday, September 13, 2013 - 4:40:09 AM

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  • HAL Id : tel-00833240, version 1

Citation

Sébastien Magnifico. Les mécanismes moléculaires de la dégénérescence axonale dans un contexte de type Dying back pattern. Neurosciences [q-bio.NC]. Université Pierre et Marie Curie - Paris VI, 2012. Français. ⟨NNT : 2012PAO66246⟩. ⟨tel-00833240⟩

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