Heterotypic interactions in amyloid function and disease. (8th February 2021)

• Record Type: Journal Article
• Authors: Konstantoulea, Katerina; Louros, Nikolaos; Rousseau, Frederic; Schymkowitz, Joost
• Is Part Of: FEBS journal. Volume 289:Number 8(2022)
• Page Start: 2025
• Page End: 2046
• Publication Date: 2021-02-08
• Subjects: aggregation‐prone regions -- amyloid co‐deposition -- amyloid polymorphism -- amyloid strains -- amyloidosis -- co‐aggregation -- cross‐seeding -- functional amyloids -- heterotypic aggregation -- phase separation -- phase transition -- prion transmissibility -- selective vulnerability -- sequence specificity -- supersaturated proteins; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.15719
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Amyloid aggregation results from the self‐assembly of identical aggregation‐prone sequences into cross‐beta‐sheet structures. The process is best known for its association with a wide range of human pathologies but also as a functional mechanism in all kingdoms of life. Less well elucidated is the role of heterotypic interactions between amyloids and other proteins and macromolecules and how this contributes to disease. We here review current data with a focus on neurodegenerative amyloid‐associated diseases. Evidence indicates that heterotypic interactions occur in a wide range of amyloid processes and that these interactions modify fundamental aspects of amyloid aggregation including seeding, aggregation rates and toxicity. More work is required to understand the mechanistic origin of these interactions, but current understanding suggests that both supersaturation and sequence‐specific binding can contribute to heterotypic amyloid interactions. Further unravelling these mechanisms may help to answer outstanding questions in the field including the selective vulnerability of cells types and tissues and the stereotypical spreading patterns of amyloids in disease. Abstract : Heterotypic interactions between amyloids, as well as with other proteins and macromolecules, contribute to a wide range of human pathologies, while hybrid amyloid complexes also serve important biological functions in all kingdoms of life. We review recent evidence on the role of sequence specificity, phase separation events and supersaturation in amyloid cross‐talk and critically speculate on possible implications to important amyloid properties, such as cellular susceptibility, prion transmissibility and polymorphism.