Karampetsou Mantia, Sykioti Vasia Samantha, Leandrou Emmanouela, Melachroinou Katerina, Lambiris Alexandros, Giannelos Antonis, Emmanouilidou Evangelia, Vekrellis Kostas
Center for Basic Research, Biomedical Research Foundation Academy of Athens, Athens, Greece.
Laboratory of Biochemistry, Department of Chemistry, National and Kapodistrian University of Athens, Athens, Greece.
Front Neurosci. 2020 Apr 21;14:246. doi: 10.3389/fnins.2020.00246. eCollection 2020.
α-Synuclein (α-syn) has been genetically and biochemically linked to the pathogenesis of Parkinson's disease (PD). There is accumulating evidence that misfolded α-syn species spread between cells in a prion-like manner and seed the aggregation of endogenous protein in the recipient cells. Exosomes have been proposed to mediate the transfer of misfolded α-syn and thus facilitate disease transmission, although the pathological mechanism remains elusive. Here, we investigated the seeding capacity of exosome-associated α-syn, . Disease-associated α-syn was present in exosome fractions isolated from transgenic A53T mouse brain. However, following intrastriatal injection of such exosomes in wild-type (wt) mice, we were not able to detect any accumulation of endogenous α-syn. In addition, recombinant fibrillar α-syn, when loaded to isolated brain exosomes, induced minor pathological α-syn brain accumulation at 7 months post injection. These data suggest that exosomes neutralize the effect of toxic α-syn species and raise additional questions on their paracrine modulatory role in disease transmission.
α-突触核蛋白（α-syn）在基因和生化方面均与帕金森病（PD）的发病机制相关。越来越多的证据表明，错误折叠的α-syn以朊病毒样方式在细胞间传播，并引发受体细胞内源性蛋白质的聚集。尽管病理机制仍不清楚，但已有研究提出外泌体可介导错误折叠的α-syn的转移，从而促进疾病传播。在此，我们研究了外泌体相关α-syn的播种能力。从转基因A53T小鼠大脑中分离的外泌体组分中存在与疾病相关的α-syn。然而，在将此类外泌体纹状体内注射到野生型（wt）小鼠后，我们未能检测到内源性α-syn的任何积累。此外，重组纤维状α-syn加载到分离的脑外泌体中后，在注射后7个月诱导了轻微的病理性α-syn脑内积累。这些数据表明外泌体可中和有毒α-syn物种的作用，并对其在疾病传播中的旁分泌调节作用提出了更多问题。
