title: Activity-dependent secretion of alpha-synuclein by enteric neurons.
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.
authors.affiliation: Inserm, U913, Nantes, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Paillusson
authors.forename: Thomas
authors.initials: T
authors.lastname: Clairembault
authors.forename: Mandy
authors.initials: M
authors.lastname: Biraud
authors.forename: Michel
authors.initials: M
authors.lastname: Neunlist
authors.forename: Pascal
authors.initials: P
authors.lastname: Derkinderen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D020126:Brefeldin A / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D017615:Enteric Nervous System / Q000166:cytology / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D007421:Intestine, Small / Q000294:innervation*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D061251:Primary Cell Culture; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D011500:Protein Synthesis Inhibitors; C497606:Snca protein, rat; D051844:alpha-Synuclein; D005576:Colforsin; D020126:Brefeldin A