Pre-amyloid oligomers budding: A metastatic mechanism of proteotoxicity
Fabrizio Bernini,Daniele Malferrari,Marcello Pignataro,Marcello Pignataro,Carlo Augusto Bortolotti,Giulia Di Rocco,Lidia Lancellotti,Maria Franca Brigatti,Rakez Kayed,Marco Borsari,Federica del Monte,Elena Castellini +11 more
TLDR
It is shown that pre-amyloid oligomers (PAO) mature to form linear and circular protofibrils, and amyloid fibers, and those can break reforming PAO that can migrate invading neighbor structures and the fragmentation using anti-fibers antibodies favored the migration of PAO.Abstract:
The pathological hallmark of misfolded protein diseases and aging is the accumulation of proteotoxic aggregates. However, the mechanisms of proteotoxicity and the dynamic changes in fiber formation and dissemination remain unclear, preventing a cure. Here we adopted a reductionist approach and used atomic force microscopy to define the temporal and spatial changes of amyloid aggregates, their modes of dissemination and the biochemical changes that may influence their growth. We show that pre-amyloid oligomers (PAO) mature to form linear and circular protofibrils, and amyloid fibers, and those can break reforming PAO that can migrate invading neighbor structures. Simulating the effect of immunotherapy modifies the dynamics of PAO formation. Anti-fibers as well as anti-PAO antibodies fragment the amyloid fibers, however the fragmentation using anti-fibers antibodies favored the migration of PAO. In conclusion, we provide evidence for the mechanisms of misfolded protein maturation and propagation and the effects of interventions on the resolution and dissemination of amyloid pathology.read more
Citations
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Getting to the Heart of Alzheimer Disease.
TL;DR: An overview of the cardiovascular links to Alzheimer disease is provided and a potential systemic profile of proteinopathies and a new hypothesis for the link between peripheral and central symptoms of heart failure and AD are suggested.
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Structural conformation and self-assembly process of p31-43 gliadin peptide in aqueous solution. Implications for celiac disease.
Maria Georgina Herrera,María Florencia Gómez Castro,Eduardo Daniel Prieto,Exequiel Barrera,Verónica I. Dodero,Sergio Pantano,Sergio Pantano,Fernando Gabriel Chirdo +7 more
TL;DR: The formation of p31‐43 nanostructures with increased β‐sheet structure may help to explain the molecular etiopathogenesis in the induction of proinflammatory effects and subsequent damage at the intestinal mucosa in CeD.
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Molecular dynamics simulations of amyloid-β(16-22) peptide aggregation at air-water interfaces.
Hisashi Okumura,Satoru G. Itoh +1 more
TL;DR: Results indicate that amyloid protofibril formation mainly occurs in the second layer, which is more soluble in water because the hydrophobic residues are covered by N- and C-terminal hydrophilic residues that are aligned well along the oligomer edge.
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Heart and Brain: Complex Relationships for Left Ventricular Dysfunction
Gianlorenzo Daniele,Stephanie DiLucia,Pier Giorgio Masci,Federica del Monte,Federica del Monte +4 more
TL;DR: This review summarizes the evidence for the established vascular/hypoperfusion model and explores the new hypothesis that configures the heart/brain axis as an organ system where similar pathogenic mechanisms exploit physiological and pathological changes.
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Real-Time 3D Imaging and Inhibition Analysis of Various Amyloid Aggregations Using Quantum Dots.
Xuguang Lin,Nuomin Galaqin,Reina Tainaka,Keiya Shimamori,Masahiro Kuragano,Taro Q.P. Noguchi,Kiyotaka Tokuraku +6 more
TL;DR: This study reports the real-time 3D-imaging and inhibition analysis of amyloid β (Aβ), tau, and α-synuclein aggregation utilizing the affinity between quantum dots (QD) and amyloids aggregates.
References
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Rakez Kayed,Elizabeth Head,Jennifer L. Thompson,Theresa M. McIntire,Saskia Milton,Carl W. Cotman,Charles G. Glabe +6 more
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Frederique Bard,Catherine Cannon,Robin Barbour,Rae Lyn Burke,Dora Games,Henry Grajeda,Teresa Guido,Kang Hu,Jiping Huang,Kelly Johnson-Wood,Karen Khan,Dora Kholodenko,Michael K. Lee,Ivan Lieberburg,Ruth Motter,Minh Nguyen,Ferdie Soriano,Vasquez Nicki J,Kim Weiss,Brent Welch,Peter Seubert,Dale Schenk,Ted Yednock +22 more
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TL;DR: The biochemical isolation of discrete amyloid-β moieties with pathophysiological properties sets the stage for a new approach to studying the molecular mechanisms of cognitive impairment in Alzheimer disease and related neurodegenerative disorders.
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