Year: 2021
Type: review
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.
Source: FEBS Journal
DOI: 10.1111/febs.15719
Institutions: VIB-KU Leuven Center for Brain & Disease Research, KU Leuven
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1512580055, G2475798000, Mapping the impact of post-translational modifications on protein aggregation., G5498576345, G5685691454, Principles of specificity in cross-aggregation interactions, Cellular handling of protein aggregation gatekeepers, G8248501640, Towards understanding the specificity of protein aggregation, G8524111995, G971389418
OpenAlex ID: W3125787691