Τίτλος:
Intrastriatal Administration of Exosome-Associated Pathological Alpha-Synuclein Is Not Sufficient by Itself to Cause Pathology Transmission
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Karampetsou, M.
Sykioti, V.S.
Leandrou, E.
Melachroinou, K.
Lambiris, A.
Giannelos, A.
Emmanouilidou, E.
Vekrellis, K.
Περιοδικό:
Frontiers in Neurosciences
Εκδότης:
Frontiers Media S.A
Λέξεις-κλειδιά:
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
DOI:
10.3389/fnins.2020.00246
