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Article Dans Une Revue FASEB Journal Année : 2013

NAD(+) acts on mitochondrial SirT3 to prevent axonal caspase activation and axonal degeneration

Sebastien Magnifico
  • Fonction : Auteur
Laure Saias
  • Fonction : Auteur
Berangere Deleglise
  • Fonction : Auteur
Eric Duplus
Devrim Kilinc
  • Fonction : Auteur
Marie-Christine Miquel
Jean-Louis Viovy
  • Fonction : Auteur
Bernard Brugg
  • Fonction : Auteur

Résumé

In chronic degenerative syndromes, neuronal death occurs over long periods, during which cells progressively lose their axons and, ultimately, their cell bodies. Although apoptosis is recognized as a key event in neuronal death, the molecular mechanisms involved in CNS axons degeneration are poorly understood. Due to the highly polarized phenotypes of CNS neurons, the different neuronal subcompartments are likely to be targeted by light repetitive and localized aggression. Such locally initiated deleterious signal transduction pathways could theoretically spread through the cytoplasm. However, where axon-degenerative signals initiate, what these early signals are, and how they lead to axon degeneration are unanswered questions that limit our understanding of neurodegenerative diseases and our ability to identify novel therapeutic targets. Using a microfluidic culture device adapted to CNS primary neurons, allowing specific access to the axonal and somatodendritic compartments, we analyzed the molecular pathways involved in axonal degeneration of differentiated neurons. We show here that local application of proapoptotic stimuli on the somatodentritic compartment triggers a dying-back pattern involving caspase-dependent axonal degeneration. Using complementary pharmacological and genetic approaches, we further demonstrate that NAD(+) and grape wine polyphenols prevent axonal apoptosis and act via mitochondrial SirT3 activation in axons.
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Dates et versions

hal-01542868 , version 1 (20-06-2017)

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Citer

Sebastien Magnifico, Laure Saias, Berangere Deleglise, Eric Duplus, Devrim Kilinc, et al.. NAD(+) acts on mitochondrial SirT3 to prevent axonal caspase activation and axonal degeneration. FASEB Journal, 2013, 27 (12), pp.4712-4722. ⟨10.1096/fj.13-229781⟩. ⟨hal-01542868⟩
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