title: Alpha-synuclein implicated in Parkinson's disease is present in extracellular biological fluids, including human plasma.
abstract: Parkinson's disease (PD) and other related disorders are characterized by the accumulation of fibrillar aggregates of alpha-synuclein protein (alpha-syn) inside brain cells. It is likely that the formation of alpha-syn aggregates plays a seminal role in the pathogenesis of at least some of these diseases, because two different mutations in the gene encoding alpha-syn have been found in inherited forms of PD. alpha-Syn is mainly expressed by neuronal cells and is generally considered to exist as a cytoplasmic protein. Here, we report the unexpected identification of alpha-syn in conditioned culture media from untransfected and alpha-syn-transfected human neuroblastoma cells, as well as in human cerebrospinal fluid and blood plasma. The method used was immunocapture by using anti-alpha-syn antibodies coupled to magnetic beads, followed by detection on Western blots. In all cases, alpha-syn was identified as a single 15 kDa band, which co-migrated with a recombinant form of the protein and reacted with five different antibodies to alpha-syn. Our findings suggest that cells normally secrete alpha-syn into their surrounding media, both in vitro and in vivo. The detection of extracellular alpha-syn and/or its modified forms in body fluids, particularly in human plasma, offers new opportunities for the development of diagnostic tests for PD and related diseases.
mesh_terms: D015153:Blotting, Western; D005110:Extracellular Space / Q000737:chemistry; D006801:Humans; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology; D051843:Synucleins; D014407:Tumor Cells, Cultured; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein