Titanium dioxide and carbon black nanoparticles disrupt neuronal homeostasis via excessive activation of cellular prion protein signaling.

Background: Epidemiological emerging evidence shows that human exposure to some nanosized materials present in the environment would contribute to the onset and/or progression of Alzheimer's disease (AD). The cellular and molecular mechanisms whereby nanoparticles would exert some adverse effects towards neurons and take part in AD pathology are nevertheless unknown.

Results: Here, we provide the prime evidence that titanium dioxide (TiO) and carbon black (CB) nanoparticles (NPs) bind the cellular form of the prion protein (PrP), a plasma membrane protein well known for its implication in prion diseases and prion-like diseases, such as AD.

Production of seedable Amyloid-β peptides in model of prion diseases upon PrP-induced PDK1 overactivation.

The presence of amyloid beta (Aβ) plaques in the brain of some individuals with Creutzfeldt-Jakob or Gertsmann-Straussler-Scheinker diseases suggests that pathogenic prions (PrP) would have stimulated the production and deposition of Aβ peptides. We here show in prion-infected neurons and mice that deregulation of the PDK1-TACE α-secretase pathway reduces the Amyloid Precursor Protein (APP) α-cleavage in favor of APP β-processing, leading to Aβ40/42 accumulation. Aβ predominates as monomers, but is also found as trimers and tetramers.

Expression of Heterologous PrP and Prion Propagation in RK13 Cells.

Cultured cells are valuable models to study prion infections at the cellular level. Unfortunately, the vast majority of cell lines are resistant to the propagation of prion agents. The rabbit epithelial RK13 cell line is among the few cell lines permissive to prion infection.

Isolation of Exosomes and Microvesicles from Cell Culture Systems to Study Prion Transmission.

Extracellular vesicles (EVs) are composed of microvesicles and exosomes. Exosomes are small membrane vesicles (40-120 nm sized) of endosomal origin released in the extracellular medium from cells when multivesicular bodies fuse with the plasma membrane, whereas microvesicles (i.e.

Prion strains are differentially released through the exosomal pathway.

Cell-to-cell transfer of prions is a crucial step in the spreading of prion infection through infected tissue. At the cellular level, several distinct pathways including direct cell-cell contacts and release of various types of infectious extracellular vesicles have been described that may potentially lead to infection of naïve cells. The relative contribution of these pathways and whether they may vary depending on the prion strain and/or on the infected cell type are not yet known.

microRNA-18b is upregulated in breast cancer and modulates genes involved in cell migration.

microRNAs are small non-coding RNAs of ~22 nucleotides that function at post-transcriptional level as negative regulators of gene expression. Aberrant expression of microRNAs could promote uncontrolled proliferation, migration and invasion of human cancer cells. In this study, we analyzed the expression of microRNA-18b (miR-18b) in breast cancer cell lines and in a set of clinical specimens.

A simple, versatile and sensitive cell-based assay for prions from various species.

Detection and quantification of prion infectivity is a crucial step for various fundamental and applied aspects of prion research. Identification of cell lines highly sensitive to prion infection led to the development of cell-based titration procedures aiming at replacing animal bioassays, usually performed in mice or hamsters. However, most of these cell lines are only permissive to mouse-adapted prions strains and do not allow titration of prions from other species.

Mammalian prions: tracking the infectious entities.

Protein misfolding is central to the pathogenesis of several neurodegenerative disorders. Among these disorders, prion diseases are unique because they are transmissible. The conversion of the host-encoded GPI-anchored PrP protein into a structurally altered form is crucially associated with the infectious and neurotoxic properties of the resulting abnormal PrP.

Recovery of small infectious PrP(res) aggregates from prion-infected cultured cells.

Prion diseases are characterized by deposits of abnormal conformers of the PrP protein. Although large aggregates of proteinase K-resistant PrP (PrP(res)) are infectious, the precise relationships between aggregation state and infectivity remain to be established. In this study, we have fractionated detergent lysates from prion-infected cultured cells by differential ultracentrifugation and ultrafiltration and have characterized a previously unnoticed PrP species.