V secretion (Faure et al. 2006). Further evidence for activity-dependent EMV release

V secretion (Faure et al. 2006). Further evidence for activity-dependent EMV release has been provided by Lachenal et al. (2011) who have demonstrated that neuronal EMV secretion is regulated by calcium influx and glutamatergic activity. Not only treatment with ionomycin to raise intracellular calcium concentrations but also increased glutamatergic activity after pharmacological inhibition of -aminobutyric acid (GABA)-A receptors results in enhanced EMV secretion from neuronal cultures. Interestingly, treatment with AMPA- or N-methyl Daspartate (NMDA)-receptor antagonists counteract the glutamatergic effect on EMV release. Hence, the authors speculate that neurons modulate their number of ionotropic postsynaptic receptors, synaptic plasticity and strength by activitydependent EMV release (Lachenal et al. 2011). In vivo evidence of neuronal exosome release and its functional significance is still lacking. The transduction of wnt signalling by exosome-like vesicular structures has been reported in Drosophila. The palmitoylated wnt proteins are membrane-bound and thus unlikely to be released as soluble proteins to the extracellular space. Instead, the Drosophila wnt1 homolog wingless (wg) has been shown to be transported trans-synaptically with vesicles resembling exosomes, followed by the binding of wg to Drosophila frizzled 2 (DFz2) receptors at the postsynapse (Korkut et al. 2009). Further in vivo evidence for neuronally derived EMVs is based on their presence in cerebrospinal fluid (CSF). Vella et al. (2008) have described the isolation of microparticles, which are enriched in the native prion protein PrPc, from ovine CSF. Harrington et al. (2009) have identified, in human CSF, nanostructures including exosome-like vesicles that can be labelled with antibodies against various exosomal marker proteins in immuno-transmission electron microscopy. Whereas these vesicles might be derived from CSF immune cells or ventricular ependymal cells, we have been able to fractionate, from human CSF, exosome-shaped vesicles positive for GluR2, indicating their neuronal origin (own unpublished data).Exosomes in neurodegenerative diseases Although definitive evidence for intercellular EMV transfer within the CNS is still lacking, EMVs have been repeatedly discussed as potential carriers in the dissemination of disease pathology in neurodegenerative disorders (for a review, see Aguzzi and Rajendran 2009).Cell Tissue Res (2013) 352:33Prions This hypothesis evolved first in the context of the interneuronal spreading of transmissible prion disorders such as the new variant of Creutzfeld-Jacob disease (CJD), bovine spongiform encephalitis (BSE) and scrapie. Prions exist in two different conformational states: the natively folded PrPc and the disease-associated misfolded PrPsc.Amantadine PrPsc is characterized by an abnormal conformation, which can serve as a template to induce the misfolding of PrPc (a mechanism called permissive templating).Oxacillin sodium salt In infectious prion diseases, PrPsc can enter the organism by the gut, followed by the invasion of lymphoid tissue from where it spreads into the peripheral nervous system and finally the CNS.PMID:26644518 In addition to intercellular transfer by tunneling nanotubes, as discussed by Gousset et al. (2009), a role for exosomes as a carrier for PrPsc in this intercellular dissemination has been proposed. Tunnelling nanotubes are transient membranous connections that can connect cells over distances of up to 100 m. Two types of nanotubes can be d.