Prion Diseases and Protein Misfolding

NG2 glia protect against prion neurotoxicity by inhibiting prostaglandin E2 signaling

This study shows NG2 glia reduce prion-induced neurodegeneration by inhibiting PGE2 signaling, which promotes microglial activation and neurotoxicity.

Estimating sequence diversity of prion protein gene (PRNP) in Portuguese populations of two cervid species: red deer and fallow deer.

The paper analyzes PRNP gene exon 3 in red and fallow deer from Portugal, finding three SNPs in red deer and no variation in fallow deer, suggesting potential susceptibility to CWD.

Standardization of Data Analysis for RT-QuIC-based Detection of Chronic Wasting Disease

This study establishes a standardized method using maxpoint ratios (MPR) to improve consistency in RT-QuIC analysis for detecting chronic wasting disease.

Therapeutic trial of anle138b in mouse models of genetic prion disease

This study tests anle138b in mouse models of prion disease, finding improved survival in RML strain models but no clear endpoints in genetic mutation models.

Characterisation and prion transmission study in mice with genetic reduction of sporadic Creutzfeldt-Jakob Disease risk gene Stx6

This study investigates the role of Stx6 in prion disease by creating a mouse model with genetic depletion of Stx6 and finding a modest effect on prion disease incubation periods.

Prion propagation is dependent on key amino acids in Charge cluster 2 within the prion protein

The paper identifies key amino acids in Charge Cluster 2 of the prion protein critical for prion propagation across multiple strains.

Identification of a cardiac glycoside exhibiting favorable brain bioavailability and potency for reducing levels of the cellular prion protein

Rapid ex vivo reverse genetics identifies the essential determinants of prion protein toxicity

This study identifies K27 as a critical residue for GDL toxicity and prion-related neurodegeneration using ex vivo reverse genetics in PrPC-deficient slices.

An Arrayed Genome-Wide Perturbation Screen Identifies the Ribonucleoprotein hnRNP K As Rate-Limiting for Prion Propagation

The paper identifies Hnrnpk as a key regulator of prion propagation through a genome-wide RNAi screen using the QUIPPER assay, showing PSA's ability to reduce prion levels and toxicity in multiple models.

Single-nuclei transcriptomics of mammalian prion diseases identifies dynamic gene signatures shared between species

This study uses single-nuclei transcriptomics to identify dynamic gene signatures in prion diseases across species.

Conformation-dependent influences of hydrophobic amino acids in two in-register parallel β-sheet amyloids, an α-synuclein amyloid and a local structural model of PrPSc

The paper investigates how hydrophobic amino acid mutations affect the stability of β-sheet amyloids in α-synuclein and a PrPSc model, revealing their role in prion strain diversity.

Transmission of Cervid Prions to Humanized Mice Demonstrates the Zoonotic Potential of CWD

This study shows CWD prions can infect humanized mice, leading to atypical symptoms and transmissible infectivity, suggesting zoonotic potential and possible human transmission.

Analysis of non-human primate models for evaluating prion disease therapeutic efficacy

The paper evaluates the feasibility of using non-human primate models to assess prion disease therapeutic efficacy by analyzing incubation times and model characteristics.

Simultaneous pathway engagement of translation in astrocytes, circadian rhythm in GABAergic neurons and cytoskeleton in glutamatergic neurons precede electroencephalographic changes in neurodegenerative prion disease

The paper identifies early translatome changes in specific neural cell types before EEG and neuropathological signs of prion disease in mice.

A conformational switch controlling the toxicity of the prion protein

This study identifies an H-latch conformational switch in PrPC that drives prion toxicity and shows that disrupting this switch can protect against prion-related neurodegeneration.

A Non-invasive, Biomarker Assay for Detecting Chronic Wasting Disease Pathology in White-tailed Deer

The paper describes a blood test using miRNA biomarkers to detect Chronic Wasting Disease in white-tailed deer, achieving high sensitivity and specificity comparable to standard methods.

Complete microglia deficiency accelerates prion disease without enhancing CNS prion accumulation

This study shows that complete microglia deficiency accelerates CNS prion disease without increasing prion accumulation, suggesting microglia protect against astrocyte-driven pathology rather than clearing prions.

A Field-Deployable Diagnostic Assay for the Visual Detection of Misfolded Prions

The paper develops a field-deployable diagnostic assay, MN-QuIC, for visual detection of misfolded prions in CWD-infected deer, showing 100% consistency with established tests.

Potential genetic robustness of Prnp and Sprn double knockout mouse embryos towards ShRNA-lentiviral inoculation

The paper investigates the transcriptomic response of Prnp and Sprn double knockout mouse embryos to ShRNA lentiviral inoculation, finding reduced apoptosis and interferon responses in the double knockout compared to single knockouts.

Universal functions of prion candidates across all three domains of life suggest a primeval role of protein self-templating.

The paper identifies candidate prions across all three domains of life and finds conserved functions suggesting ancient roles in adaptation and evolution.

Activation of IP10/CXCR3 signaling with highly coincidental with PrPSc deposit in the brains of scrapie infected mice

The paper shows IP10/CXCR3 signaling is activated in prion-infected mice brains, coinciding with PrPSc deposits, suggesting it as a potential therapeutic target.

New Drosophila models to uncover the intrinsic and extrinsic factors mediating the toxicity of the human prion protein

The paper introduces a Drosophila model expressing human PrP to study intrinsic and extrinsic factors mediating its toxicity, identifying key cellular mechanisms and protective mutations.

Primary glia cells from bank vole propagate multiple rodent-adapted scrapie prions

This study develops a bank vole glia cell assay that can propagate multiple rodent-adapted scrapie prions, showing comparable or faster propagation than traditional host cell models.

Ligands binding to the cellular prion protein induce its protective proteolytic release with therapeutic potential in neurodegenerative proteinopathies

The paper shows that ligands binding to PrPC induce its proteolytic release, which has neuroprotective effects, and identifies mechanisms and exceptions in this process.

Highly efficient intercellular spreading of protein misfolding mediated by viral ligand - receptor interactions

The paper shows viral ligand-receptor interactions enhance the spread of protein misfolding via extracellular vesicles and direct cell contact.

RT-QuIC detection of CWD prion seeding activity in white-tailed deer muscle tissues

This study uses RT-QuIC to detect CWD prion seeding activity in skeletal muscles of infected white-tailed deer, finding prions in consumption-relevant tissues and highlighting their broader distribution.

Loss of PIKfyve drives the spongiform degeneration in prion diseases

The paper shows that loss of PIKfyve contributes to spongiform degeneration in prion diseases by linking prion infection to PIKfyve destabilization and vacuolation.

Characterizing the demographic history and prion protein variation to infer susceptibility to chronic wasting disease in a naïve population of white-tailed deer (Odocoileus virginianus)

The paper assesses genomic variation and PRNP gene diversity in white-tailed deer to infer susceptibility to chronic wasting disease and demographic history.

Behavioral deficits, learning impairment, and enhanced hippocampal excitability in co-isogenic PrnpZH3/ZH3 mice

This study investigates the role of PrPC in hippocampal function using PrnpZH3/ZH3 mice, finding behavioral deficits, learning impairment, and increased excitability without enhanced LTP.

Novel regulators of PrPC biosynthesis revealed by genome-wide RNA interference

This paper identifies 54 novel regulators of PrPC expression through a genome-wide RNA interference screen, with 9 confirmed by CRISPR interference, revealing potential therapeutic targets for prion diseases.