Parkinsons disease (PD) is a chronic progressive neurodegenerative disease which was first described in 1817, affecting 1% of population over 60 years old.And it is a part of a subset of diseases classified as protein-misfolding disorders (PMDs), which also includes Alzheimers disease, Huntington disease, and amyotrophic lateral sclerosis (ALS).PMDs share common patho-logical features, characterized by the accumulation of abnormal protein inclusions and oligomers of an underlying protein.α-synuclein , as the first gene identified in PD is the main component of the neuropathological hallmark of the intracellular inclusions called Lewybobies (LBs).Many studies have suggested that α-synuclein acts as a molecular chaperoneintercellularly.For example, it can promote SNARE-complex assembly in vivo and in vitro by binding to the SNARE-protain synaptobrevin-2/vesicle-associated membrane protain 2 (VAMP 2).Also, the N-terminal domain (residues 1-65) of α-synuclein can adopt an α-helical conformation and interact with the surface of micells and membranes.Since human α-synucleinpurieied from red blood cells as a tetramer, it maybe work as a regulator of membrane fluidity.However, the real physiological and pathological functions of α-synuclein remain unknown.Exsomes, the small membranous vesicles released from many typies of mammalian cells, have played an necessary role in cell-cell signaling, removingnonnecessaryprotains and trandferring pathogens for instance, prions, between-cells.Exosome biogenesis involves the inwarding budding of endosomes to form multivesicular bodies (MVB).When fused with the plasma membrane, the MVB releases the vesicles into the extracellular spaces as exsomes.However, El-Agnaf et al.showed that α-synuclein species can be detected in human plasma and CSF and also in the medium of cultured neuronal cells.So many attentions are paid to the function and mechanism of the secreted α-synuclein by exsomes.Evangeliaetal.suggested that α-synuclein could be secreted via exsomes constitutively and physio-logically.And in this study, they supported a calcium-dependent manner through which α-synuclein was secreted into extracellular environment.Since calcium is fundamental in regulating exocytosis, early endosome fusion, and exosome-mediated release, it maybe an important factor in the mechanism of secretion.They also proved that the level of calcium, especially the level of intracellular calcium affected the secreted α-synuclein by exosomes.Furthermore, the medium containing secreted α-synuclein was toxic to recipient neuronal cells, which perhaps supported the hypothesis that neurodegeneration results from the progressive propagation of pathogenic events, cell by cell,throughout brain area.In addition, the main dopaminergic midbrain subpopulation affected in PD is a subpopulation of A9 nigrostriatal neurons, which are calbindin D28K-negative but G-protein-coupled inwardly-rectifying potassium channel 2 (GIRK2)-positive, andthe pacemaker activity of adult SNc dopaminergic neurons is driven by L-type CaV1.3 calcium channels, in contrast to sodium channels in VTA neurons, which could place SNc neurons under higher risk from calcium-dependent neurotoxic processes than those of VTA.By an interesting coincidence, α-synuclein is secreted in a calcium-dependent manner, which maybe indicate the degeneration is, at least in part, related to the decreased ability to buffer cytosolic calcium levels.Also, Lydia et al.demonstratede that lysosomal dysfunction through ammonium chloride or bafilomycin A1 led to an increase in the release of α-synuclein in exosomes and a concomitant increase in α-synuclein transmission to recipient cells.In a way, this study proved the importance of exosomes in the release of α-synuclein and its transmission between cell and cell.To supplement the circuit of α-synuclein secretion and internalization, researches about the mechanism of internalization of α-synuclein have supported that glucosyltransferase inhibitor or proteinase K inhibited the internalization of extracellular monomeric α-synuclein into BV-2 cells,and that monosialoganagliosideGM1 improved the inhibition.Moreover,they also observed the mechanism was a lipid raft-dependent pattern, but the exact mechanism is unclear.In conclusion, secreted α-synuclein in exosomes may be one of the cardinal factors involved in PD.Exosomes release with cytocolicnonnecessary proteins into extracellular spaces, there, some of the protein are internalized by neighouboringcells.In a sense,dysfunction of each part of the secretion and internalization pathway potentially leads to the accumulation of proteins intracellular or extracellular.So, it should be greatly helpful to discovery the pathogenesis of PD, if the real mechanism has been found out.