Analysis of molecular mechanisms behind the prion hypothesis in synucleinopathy

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The intracellular deposition of misfolded proteins is a common neuropathological hallmark of most neurodegenerative disorders. Increasing evidence suggests that these pathogenic proteins may spread to neighboring cells and induce the propagation of neurodegeneration. In this study, we showed that unlike prion protein, extracellular alpha-synuclein (aS), a major constituent of intraneuronal inclusions in Parkinson's disease, was mainly recovered in the supernatant fraction rather than in exosome-containing pellets from the neuronal culture medium and cerebrospinal fluid. In addition, we identified that the extracellular secretion of aS was secreted via Rab11-mediated recycling pathway (Hasegawa T, et al., PloS One 2011). Furthermore, we demonstrated that aSwas taken up by neuronal and oligodendroglial cells bu dynamic-dependent endocytosis (Konno M, et al., Mol Neurodegener 2012).