Articles by Margaret M. P. Pearce in JoVE
Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster Kirby M. Donnelly1, Margaret M. P. Pearce1 1Department of Biological Sciences, University of the Sciences Accumulating evidence supports the idea that pathogenic protein aggregates associated with neurodegenerative diseases spread between cells with prion-like properties. Here, we describe a method that enables visualization of cell-to-cell spreading of prion-like aggregates in the model organism, Drosophila melanogaster.
Other articles by Margaret M. P. Pearce on PubMed
Prion-like Transmission of Pathogenic Protein Aggregates in Genetic Models of Neurodegenerative Disease Current Opinion in Genetics & Development. Jun, 2017 | Pubmed ID: 28441621 A key pathological hallmark of most neurodegenerative diseases is the misfolding of a particular protein, leading to deposition of toxic protein aggregates in brain tissue. Recent data provide compelling evidence that pathogenic protein aggregates have prion-like properties-they self-replicate by templated misfolding of monomeric proteins and spread between individual cells. Studies in genetic model organisms have expanded our understanding of how prion-like pathogenic aggregates propagate in vivo, revealing potential roles for spreading along neural networks and key cellular processes in both neurons and glial cells. These findings and future studies in genetic models will help guide the development of novel therapeutic strategies that directly target the molecular mechanisms underlying these devastating diseases.
Prion-Like Characteristics of Polyglutamine-Containing Proteins Cold Spring Harbor Perspectives in Medicine. Feb, 2018 | Pubmed ID: 28096245 Transmissible spongiform encephalopathies are infectious neurodegenerative diseases caused by the conversion of prion protein (PrP) into a self-replicating conformation that spreads via templated conversion of natively folded PrP molecules within or between cells. Recent studies provide compelling evidence that prion-like behavior is a general property of most protein aggregates associated with neurodegenerative diseases. Many of these disorders are associated with spontaneous protein aggregation, but genetic mutations can increase the aggregation propensity of specific proteins, including expansion of polyglutamine (polyQ) tracts, which is causative of nine inherited neurodegenerative diseases. Aggregates formed by polyQ-expanded huntingtin (Htt) in Huntington's disease can transfer between cells and seed the aggregation of cytoplasmic wild-type Htt in a prion-like manner. Additionally, prion-like properties of glutamine-rich proteins underlie nonpathological processes in yeast and higher eukaryotes. Here, we review current evidence supporting prion-like characteristics of polyQ and glutamine-rich proteins.