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Infectious Prions Are Associated with Morphologically Distinct Exosomes

At the 2013 annual International Society for Extracellular Vesicles (ISEV) ( conference held in Boston, April 17-20, Andrew Hill, Ph.D., Professor in the Department of Biochemistry and Molecular Biology, at the Bio21 Institute, University of Melbourne in Australia, delivered an oral presentation entitled “Infectious Prions Are Associated with Morphologically Distinct Exosomes.” Exosomes (image) are tiny subcellular membrane-bound vesicles (30-150 nm in diameter) that are released by a wide variety of normal cell types and cancer cells, and that can carry membrane and cellular proteins, as well as microRNA (miRNA), and various other types of RNA, including mRNA fragments, representative of the cell of origin. It is thought that exosomes may serve the purpose of shuttling information from one cell to another. For instance, it has been shown that exosomes can carry material from cancer cells that acts to suppress the immune system and stimulate angiogenesis, thus encouraging cancer growth. In his presentation, Dr. Hill first showed evidence that PrPC (non-infectious) and PrPSc (infectious) forms of the prion protein are both associated with exosomes. He also demonstrated using cryo-electron microscopy that prion-infected cells release exosomes with distinct ultrastructural features and that prion-containing exosomes are more effective at transmitting prion infection than are cell extracts. Dr. Hill also showed that small RNA deep sequencing revealed a distinct miRNA profile in exosomes from prion-infected cells. This sequencing was carried out using the SOLiD® platform and also the Ion Torrent™ platform from Life Technologies. This analysis showed nine miRNAs to be dysregulated in the exosomes from prion-infected cells versus miRNAs in the exosomes from controls. Based on these results, Dr. Hill posed the question of whether “we can use exosomal miRNA profiles to diagnose neurodegenerative diseases.” He went on to show that deep sequencing of exosomal RNA from Alzheimer’s disease blood samples reveals specific miRNA signatures that may offer the potential for use in diagnostics. He emphasized that this approach may have much broader application, both to other neurodegenerative diseases, and to other types of disease altogether. [ISEV conference web site] [ISEV conference blog]