title: Cross-linking for the analysis of α-synuclein in the enteric nervous system.
abstract: Since the observation that aggregated α-synuclein, the pathological hallmark of Parkinson's disease (PD), is found in the gut in almost all patients, it has been suggested that the enteric nervous system (ENS) could be a starting point for α-synuclein pathology. α-synuclein has long been thought to occur as a monomer in living cells, but recent studies reported that it instead exists as a tetramer in non-neuronal cells and in neurons. Given the possible key role of the ENS in PD pathophysiology, we undertook the current research to characterize the native state of α-synuclein in rat primary culture of ENS and in adult human healthy ENS. Using amine-reactive cross-linking, we showed that, by contrast to cell lines and brain neurons, α-synuclein exists primarily as a monomer in intact enteric neurons, suggesting that the native state of α-synuclein is different between the ENS and the brain. Our results provide new insights into the widely discussed concepts of α-synuclein aggregation and misfolding in PD and raise issue about the possible transmission of α-synuclein from the ENS to the brain.
authors.affiliation: Inserm, U913, Nantes, France.|Nantes University, Nantes, France.|Department of Neurology, CHU Nantes, Nantes, France.
authors.forename: Anne-Gaëlle
authors.initials: AG
authors.lastname: Corbillé
authors.affiliation: Inserm, U913, Nantes, France.|Nantes University, Nantes, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Neunlist
authors.affiliation: Inserm, U913, Nantes, France.|Nantes University, Nantes, France.|Department of Neurology, CHU Nantes, Nantes, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Derkinderen
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017615:Enteric Nervous System / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein
keywords: Parkinson's disease; cross-linking; enteric nervous system; α-synuclein