Activity-dependent secretion of alpha-synuclein by enteric neurons

Authors

  • Sébastien Paillusson,

    1. Inserm, U913, Nantes, France
    2. University Nantes, Nantes, France
    3. CHU Nantes, Institut des Maladies de l'Appareil Digestif, Nantes, France
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  • Thomas Clairembault,

    1. Inserm, U913, Nantes, France
    2. University Nantes, Nantes, France
    3. CHU Nantes, Institut des Maladies de l'Appareil Digestif, Nantes, France
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  • Mandy Biraud,

    1. Inserm, U913, Nantes, France
    2. CHU Nantes, Institut des Maladies de l'Appareil Digestif, Nantes, France
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  • Michel Neunlist,

    1. Inserm, U913, Nantes, France
    2. University Nantes, Nantes, France
    3. CHU Nantes, Institut des Maladies de l'Appareil Digestif, Nantes, France
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  • Pascal Derkinderen

    Corresponding author
    1. University Nantes, Nantes, France
    2. CHU Nantes, Institut des Maladies de l'Appareil Digestif, Nantes, France
    3. Department of Neurology, CHU Nantes, France
    • Inserm, U913, Nantes, France
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Address correspondence and reprint requests to Pascal Derkinderen, Inserm U913, 1, place Alexis Ricordeau 44093 Nantes Cedex 1, France. E-mails: derkinderenp@yahoo.fr; pascal.derkinderen@chu-nantes.fr

Abstract

There is growing evidence supporting a role of extracellular alpha-synuclein in the spreading of Parkinson's disease (PD) pathology. Recent pathological studies have raised the possibility that the enteric nervous system (ENS) is one of the initial sites of alpha-synuclein pathology in PD. We therefore undertook this survey to determine whether alpha-synuclein can be secreted by enteric neurons. Alpha-synuclein secretion was assessed by immunoblot analysis of the culture medium from primary culture of ENS. We show that alpha-synuclein is physiologically secreted by enteric neurons via a conventional, endoplasmic reticulum/Golgi-dependent exocytosis, in a neuronal activity-regulated manner. Our study is the first to evidence that enteric neurons are capable of secreting alpha-synuclein, thereby providing new insights into the role of the ENS in the pathophysiology of PD.

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