title: Assessment of α-synuclein secretion in mouse and human brain parenchyma.
abstract: Genetic, biochemical, and animal model studies strongly suggest a central role for α-synuclein in the pathogenesis of Parkinson's disease. α-synuclein lacks a signal peptide sequence and has thus been considered a cytosolic protein. Recent data has suggested that the protein may be released from cells via a non-classical secretory pathway and may therefore exert paracrine effects in the extracellular environment. However, proof that α-synuclein is actually secreted into the brain extracellular space in vivo has not been obtained. We developed a novel highly sensitive ELISA in conjugation with an in vivo microdialysis technique to measure α-synuclein in brain interstitial fluid. We show for the first time that α-synuclein is readily detected in the interstitial fluid of both α-synuclein transgenic mice and human patients with traumatic brain injury. Our data suggest that α-synuclein is physiologically secreted by neurons in vivo. This interstitial fluid pool of the protein may have a role in the propagation of synuclein pathology and progression of Parkinson's disease.
authors.affiliation: Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Emmanouilidou
authors.forename: Dimitris
authors.initials: D
authors.lastname: Elenis
authors.forename: Themis
authors.initials: T
authors.lastname: Papasilekas
authors.forename: Georgios
authors.initials: G
authors.lastname: Stranjalis
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Gerozissis
authors.forename: Penelopi C
authors.initials: PC
authors.lastname: Ioannou
authors.forename: Kostas
authors.initials: K
authors.lastname: Vekrellis
mesh_terms: D000328:Adult; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D045604:Extracellular Fluid / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017551:Microdialysis; D008875:Middle Aged; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein