@article{discovery10073714,
         journal = {Journal of Biological Chemistry},
           title = {Prion protein stabilizes amyloid-{\ensuremath{\beta}} (A{\ensuremath{\beta}}) oligomers and enhances A{\ensuremath{\beta}} neurotoxicity in a Drosophila model of Alzheimer's disease},
           pages = {13090--13099},
            note = {This version is the version of record. For information on re-use, please refer to the publisher's terms and conditions.},
          volume = {293},
            year = {2018},
          number = {34},
           month = {August},
        abstract = {The cellular prion protein (PrPC) can act as a cell-surface receptor for {\ensuremath{\beta}}-amyloid (A{\ensuremath{\beta}}) peptide; however, a role for PrPC in the pathogenesis of Alzheimer's disease (AD) is contested. Here, we expressed a range of A{\ensuremath{\beta}} isoforms and PrPC in the Drosophila brain. We found that co-expression of A{\ensuremath{\beta}} and PrPC significantly reduces the lifespan, disrupts circadian rhythms, and increases A{\ensuremath{\beta}} deposition in the fly brain. In contrast, under the same conditions, expression of A{\ensuremath{\beta}} or PrPC individually did not lead to these phenotypic changes. In vitro studies revealed that substoichiometric amounts of PrPC trap A{\ensuremath{\beta}} as oligomeric assemblies and fragment-preformed A{\ensuremath{\beta}} fibers. The ability of membrane-anchored PrPC to trap A{\ensuremath{\beta}} as cytotoxic oligomers at the membrane surface and fragment inert A{\ensuremath{\beta}} fibers suggests a mechanism by which PrPC exacerbates A{\ensuremath{\beta}} deposition and pathogenic phenotypes in the fly, supporting a role for PrPC in AD. This study provides a second animal model linking PrPC expression with A{\ensuremath{\beta}} toxicity and supports a role for PrPC in AD pathogenesis. Blocking the interaction of A{\ensuremath{\beta}} and PrPC represents a potential therapeutic strategy.},
        keywords = {Alzheimer's disease, Drosophila, amyloid-beta (AB), animal model, circadian rhythm, fibril, neurodegenerative disease, oligomer, prion, protein misfolding, Alzheimer Disease, Amyloid, Amyloid beta-Peptides, Animals, Circadian Rhythm, Disease Models, Animal, Drosophila melanogaster, Longevity, Mesocricetus, Neurotoxicity Syndromes, Prion Proteins, Protein Binding, Protein Multimerization},
             url = {https://doi.org/10.1074/jbc.RA118.003319},
            issn = {1083-351X},
          author = {Younan, ND and Chen, K-F and Rose, R-S and Crowther, DC and Viles, JH}
}