Ckaging and release from cells. In vivo, we administered exosomes through nasal delivery, a system we’ve got previously identified to provide functional exosomes for the brain. In both wild form and -synuclein transgenic mouse brains we observed Lewy body-like aggregates following delivery of exosomes containing -synuclein. Delivery of control exosomes did not result in brain aggregates, similarly, delivery of -synuclein containing exosomes to -synuclein knockout mice did not result in brain aggregates. Behavioural testing showed that animals provided synuclein containing exosomes had movement deficits in their hind limbs, whereas animals given control exosomes or -synuclein exosomes to knockout mice did not display any behavioural deficits. Summary/Conclusion: Right here we identified a mechanistic pathway for the packaging of -synuclein into exosomes and show that these exosomes are capable to propagate aggregated forms in the protein to the brains of rodents. These findings show how exosomes can transmit -synuclein in the brain resulting in Lewy body-like aggregates and movement deficits which can be identified in Parkinson’s disease. Funding: This work was funded by NHMRC project grants awarded to J Howitt.Friday, 04 MaySymposium Session 13 – Part of Tumour EVs in Cell-Cell Communication Chairs: Antonella Bongiovanni; Hector Peinado Place: Auditorium 13:45 – 15:OF13.Laptop or computer guided image analysis of nuclear membrane instability in tissues reveals clinical relevance for nucleus-derived EVs Tatiana Novitskya1; Adel Eskaros1; Mariana Reis-Sobreiro2; Michael R Freeman2; Dolores Di Vizio2; Andries ZijlstraDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Health-related Center, Nashville, TN, USA; 2Departments of Surgery, Biomedical Sciences, and Pathology and Laboratory Medicine, Tissue Inhibitor of Metalloproteinase (TIMPs) Proteins Biological Activity Cedars-Sinai Health-related Center, Los Angeles, CA, USABackground: Although it really is properly established that Hepatitis C virus E1 Proteins supplier oncogenic transformation causes cells to shed a heterogeneous population extracellular vesicles (EV), trusted techniques for evaluating and quantifying the biogenesis of EV in patient tissue have already been lacking. In prior studies of prostate cancer, we observed comprehensive EV shedding and enhanced malignant behaviour in cancer cells that exhibit nuclear instability. Nuclear blebbing and shedding of EV containing genomic material might be detected in tumour tissue from experimental models of nuclear membrane instability generated by depletion of your cytoskeletal regulator DIAPH3 or nuclear lamin A/C. To decide the clinical significance of this mechanism in prostate cancer, we developed a novel approach for the quantitative analysis of EV production in formalin-fixed paraffinembedded clinical tissues. Methods: To visualize release of nucleus-derived particles, multiplex immunofluorescent detection of nuclear histone, DNA and nuclear envelope (Emerin) collectively with the epithelial cytokeratin (CK18) was performed on a tissue microarray containing tumour, adjacent benign and metastatic LN tissue (n = 80). Machine studying was leveraged, for the first time, to develop an image evaluation pipeline that enabled singlecell segmentation and quantitation of nucleus-derived EV linked with nuclear membrane instability. Outcomes: Nucleus-derived EV was evident in 50 of prostate cancer individuals and 80 of tumour-involved lymph nodes. Intra-patient variations in particle size, location and enumeration recommend that substantial variation inside the mechanisms of biogenesis may exist. Most importantl.