Dical Center Hamburg Eppendorf UKE, ZNMH, Hamburg, GermanyPF07.Plasma-derived extracellular vesicles contain mutant SOD1 in hSOD1G93A transgenic swine Elena Berrone1; Paola Crociara1; Monica Lo Faro1; Elena Vallino Costassa1; Alessandra Favole1; Maria Chiara Deregibus2; Giovanni Camussi3; Cesare Galli4; Roberto Dopamine Receptor Agonist review Duchi4; Adriano Chi; Andrea Calvo5; Federico Casale5; Giuseppe Fuda5; Giovanni De Marco5; Cristina Casalone1; Cristiano Corona1 Istituto Zooprofilattico Sperimentale del Piemonte Liguria e Valle d’Aosta, Turin, Italy; 2University of Turin, Turin, Italy; 3Department of Medical Sciences, University of Turin, Turin, Italy; 4Avantea srl, Laboratory of Reproductive Technologies, Cremona, Italy; 5CRESLA, Regional ALS Reference Centre for Piemonte Area, Turin, ItalyBackground: Two objectives of amyotrophic lateral sclerosis (ALS) investigation are (a) validation of new experimental models and (b) identification of diagnostic biomarkers, in order to speed up the diagnosis, to monitor its progression and to assess regardless of whether a new therapy could be effective.Background: Conformational conversion and spreading from the cellular prion protein (PrPC) is crucial to prion disease pathophysiology. PrPC is actually a GPI-anchored cell surface protein, has a fast turnover and is lastly degraded in acidic lysosomes. Alternatively, PrPC may be either recycled back towards the cell surface or secreted for the extracellular space via exosomes. Regulation of PrPC turnover and sorting into exosomes will not be fully understood. Because each PrPC membrane at the same time as exosome levels influence conversion to and spreading of the misfolded protein isoform PrPSc, PrP turnover could critically influence prion disease progression. Neuronal PrPC vesicle EZH2 Inhibitor custom synthesis transport will depend on kinesin-1 and cytoplasmic dynein, but regulatory mechanisms that specify and control PrP intracellular trafficking are nonetheless unknown. Considering the fact that muskelin associates with motor protein complexes, we wanted to address whether or not muskelin might influence the regulation of PrP trafficking. Solutions: We transfected culture cells with PrP- and muskelin-reporter constructs to establish interaction and co-localization of each proteins. Muskelin-knockout (KO) mice and principal neurons of those mice have been employed to confirm our findings in vivo and to decide the influence of muskelin on prion disease pathophysiology. Outcomes: Main neurons from muskelin-KO mice show impaired transport of PrPC vesicles, PrPC lysosomal targeting and degradation. As a consequence, muskelin-KO results in elevated levels of PrPC in the plasma membrane and improved packaging of PrPC into exosomes. In contrast, overexpression of muskelin led to reduction of exosomal PrP levels. Interestingly, overall exosome secretion remains unchanged. Infection of muskelin-KO mice with prions leads to significantly accelerated prion illness. Summary/Conclusion: We could determine muskelin as a regulator of PrP sorting that is certainly affecting its levels at the plasma membrane and on exosomes, thereby substantially influencing prion illness pathophysiology. Funding: This operate was supported by Werner-Otto-Stiftung.ISEV 2018 abstract bookPF07.Study of retinal-extracellular vesicles in a model of retinitis pigmentosa: the rd10 mouse Lorena Vidal1; Maria Oltra1; Ayse Sahaboglu2; Jorge Barcia1; Sancho JavierCatholic University of Valencia, Valencia, Spain; 2University of Tuebingen Institute for Ophthalmic Analysis, Thuringen, GermanyP. Only lowered concentration of PAC-1+ CD61+ was observed [16 (1326) n/ vs.