Joel C. Watts

PRNP mutations initially generate an alternatively misfolded PrP species that dissuades prion replication

The paper identifies an alternatively misfolded PrP species, PrPAM, generated by PRNP mutations that may initially protect against prion replication, explaining delayed disease onset.

Glycogen Synthase Kinase-3β Regulates Cellular Prion Protein Levels

This study identifies GSK-3β as a regulator of PrPC levels through post-translational mechanisms and shows its impact on PrPSc levels in prion-infected cells.

Differently sized soluble α-synuclein species from multiple system atrophy and Lewy body disease brains display different seeding propensities

This study compares soluble α-synuclein species from MSA and LBD brains, finding differences in their seeding activity and size distribution.

A self-complementary recombinant adeno-associated virus vector coding for an anchorless prion protein carrying the G127V mutation extends survival in a rodent prion disease model

This paper demonstrates that delivering a protective prion protein variant via gene therapy extends survival in a prion disease mouse model.

α-Synuclein strain homogeneity in multiple system atrophy clinical subtypes

This study investigates whether distinct α-synuclein strains contribute to clinical subtypes of multiple system atrophy (MSA) and finds no differences in strain properties between MSA-C and MSA-P.

Stochastic Misfolding Drives the Emergence of Distinct α-Synuclein Strains

This study shows that stochastic misfolding leads to the formation of distinct α-synuclein strains both in vitro and in vivo, resulting in different disease phenotypes.

The Protein Disulfide Isomerase P4HB/PDIA1 Modulates PrPC Levels and Prion Replication

This study shows that P4HB/PDIA1 modulates PrPC levels and prion replication by stabilizing PrPC and acting as a chaperone in CAD5 cells.

α-Synuclein purification significantly impacts seed amplification assay performance and consistency

This study compares four methods of purifying α-synuclein for seed amplification assays, finding that osmotic shock-purified monomer has the lowest aggregation propensity and best inter-batch reproducibility.

Alternative splicing generates a Ribosomal Protein S24 isoform induced by neuroinflammation and neurodegeneration

The paper identifies Rps24c/S24-PKE as a novel marker for neuroinflammation and neurodegeneration through cell type-specific alternative splicing in mouse brains.

The Brain Interactome of a Permissive Prion Replication Substrate

The paper compares the interactomes of mouse and bank vole prion proteins in brain tissue to determine if differences in protein interactions explain the bank vole's susceptibility to prions.

The Molecular Determinants of a Universal Prion Acceptor

The paper identifies key amino acid residues in bank vole prion protein (BVPrP) that enable it to act as a universal prion acceptor, revealing molecular mechanisms for cross-species prion replication.

α-Synuclein strain propagation is independent of cellular prion protein expression in transgenic mice

This study shows that PrPC expression does not significantly affect α-synuclein strain propagation, neuroinvasion, or evolution in transgenic mice.

Convergent generation of atypical prions in knock-in mouse models of genetic prion disease

This study shows that knock-in mice with specific prion protein mutations spontaneously develop prion disease, producing atypical prion strains with similar properties regardless of mutation type.

Somatostatin slows Aβ plaque deposition in aged APPNL-F/NL-F mice by blocking Aβ aggregation in a neprilysin-independent manner

This study shows that somatostatin reduces Aβ plaque formation in aged mice by inhibiting Aβ aggregation, independent of neprilysin.

A novel approach to evaluate alpha-synuclein seeding shows a wide heterogeneity in multiple system atrophy

This study introduces a modified Real-Time Quaking-induced Conversion assay to assess alpha-synuclein seeding activity in multiple system atrophy, revealing heterogeneity in seeding behavior across brain regions.