11 research outputs found
Proteasomes and ubiquitin are involved in the turnover of the wild-type prion protein
Prion diseases propagate by converting a normal glycoprotein of the host, PrP(C), into a pathogenic ‘prion’ conformation. Several misfolding mutants of PrP(C) are degraded through the ER-associated degradation (ERAD)–proteasome pathway. In their infectious form, prion diseases such as bovine spongiform encephalopathy involve PrP(C) of wild-type sequence. In contrast to mutant PrP, wild-type PrP(C) was hitherto thought to be stable in the ER and thus immune to ERAD. Using proteasome inhibitors, we now show that ∼10% of nascent PrP(C) molecules are diverted into the ERAD pathway. Cells incubated with N-acetyl-leucinal-leucinal-norleucinal (ALLN), lactacystin or MG132 accumulated both detergent-soluble and insoluble PrP species. The insoluble fraction included an unglycosylated 26 kDa PrP species with a protease-resistant core, and a M(r) ‘ladder’ that contained ubiquitylated PrP. Our results show for the first time that wild-type PrP(C) molecules are subjected to ERAD, in the course of which they are dislocated into the cytosol and ubiquitylated. The presence of wild-type PrP molecules in the cytosol may have potential pathogenic implications
Enhanced Functional Integration of Human Photoreceptor Precursors into Human and Rodent Retina in an Ex Vivo
Influence of Iron Oxide Nanoparticles on Innate and Genetically Modified Secretion Profiles of Mesenchymal Stem Cells
Differentiation of Human Embryonic Stem Cells Using Size-Controlled Embryoid Bodies and Negative Cell Selection in the Production of Photoreceptor Precursor Cells
Associating Biological Activity and Predicted Structure of Antimicrobial Peptides from Amphibians and Insects
Antimicrobial peptides (AMPs) are a diverse class of short, often cationic biological molecules that present promising opportunities in the development of new therapeutics to combat antimicrobial resistance. Newly developed in silico methods offer the ability to rapidly discover numerous novel AMPs with a variety of physiochemical properties. Herein, using the rAMPage AMP discovery pipeline, we bioinformatically identified 51 AMP candidates from amphibia and insect RNA-seq data and present their in-depth characterization. The studied AMPs demonstrate activity against a panel of bacterial pathogens and have undetected or low toxicity to red blood cells and human cultured cells. Amino acid sequence analysis revealed that 30 of these bioactive peptides belong to either the Brevinin-1, Brevinin-2, Nigrocin-2, or Apidaecin AMP families. Prediction of three-dimensional structures using ColabFold indicated an association between peptides predicted to adopt a helical structure and broad-spectrum antibacterial activity against the Gram-negative and Gram-positive species tested in our panel. These findings highlight the utility of associating the diverse sequences of novel AMPs with their estimated peptide structures in categorizing AMPs and predicting their antimicrobial activity
NLRP3 inflammasome activation drives bystander cone photoreceptor cell death in a P23H rhodopsin model of retinal degeneration
Intercellular propagated misfolding of wild-type Cu-Zn superoxide dismutase
Abstract of the a poster presented at Prion 2013, May 26-29 Banff, Alberta, Canada