TY - JOUR
TI - Intrastriatal Administration of Exosome-Associated Pathological Alpha-Synuclein Is Not Sufficient by Itself to Cause Pathology Transmission
AU - Karampetsou, M.
AU - Sykioti, V.S.
AU - Leandrou, E.
AU - Melachroinou, K.
AU - Lambiris, A.
AU - Giannelos, A.
AU - Emmanouilidou, E.
AU - Vekrellis, K.
JO - Frontiers in Neurosciences
PY - 2020
VL - 14
TODO - null
SP - null
PB - Frontiers Media S.A
SN - 1662-4548
TODO - 10.3389/fnins.2020.00246
TODO - alpha synuclein;  recombinant alpha synuclein;  recombinant protein;  unclassified drug, animal cell;  animal experiment;  animal model;  animal tissue;  Article;  brain tissue;  controlled study;  disease transmission;  exosome;  in vivo study;  knockout mouse;  male;  mouse;  neuropathology;  nonhuman;  paracrine signaling;  Parkinson disease;  proteinosis;  transgenic mouse;  wild type mouse
TODO - 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. © Copyright © 2020 Karampetsou, Sykioti, Leandrou, Melachroinou, Lambiris, Giannelos, Emmanouilidou and Vekrellis.
ER -