Analysis of molecular mechanisms behind the prion hypothesis in synucleinopathy

错误折叠的蛋白质在细胞内沉积是大多数神经退行性疾病的共同神经病理学特征。越来越多的证据表明，这些致病蛋白可能扩散到邻近细胞，并诱导神经变性的传播。在这项研究中，我们发现，细胞外α-突触核蛋白(AS)是帕金森病神经元内包涵体的主要成分，而不是神经元培养液和脑脊液中含有外体的小球，而不是普恩蛋白。此外，我们还发现AS的胞外分泌是通过Rab11介导的循环途径分泌的(Hasegawa T等人，PLOS One 2011)。此外，我们还证明了AsS通过动态依赖的内吞作用被神经元和少突胶质细胞摄取(Konno M等人，Mol Neurodegener 2012)。

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).