AUTHOR=Karampetsou Mantia , Sykioti Vasia Samantha , Leandrou Emmanouela , Melachroinou Katerina , Lambiris Alexandros , Giannelos Antonis , Emmanouilidou Evangelia , Vekrellis Kostas TITLE=Intrastriatal Administration of Exosome-Associated Pathological Alpha-Synuclein Is Not Sufficient by Itself to Cause Pathology Transmission JOURNAL=Frontiers in Neuroscience VOLUME=14 YEAR=2020 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2020.00246 DOI=10.3389/fnins.2020.00246 ISSN=1662-453X ABSTRACT=

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, in vivo. 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.