Emerging biophysical origins and pathogenic implications of amyloid oligomers
Abstract The amyloid hypothesis has been a leading narrative concerning the pathophysiological foundation of Alzheimer’s and Parkinson’s disease. At the two ends of the hypothesis lie the functional protein monomers and the pathology-defining amyloid fibrils, while the early stages of protein aggreg...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58335-y |
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| _version_ | 1850063908911448064 |
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| author | Huayuan Tang Nicholas Andrikopoulos Yuhuan Li Stone Ke Yunxiang Sun Feng Ding Pu Chun Ke |
| author_facet | Huayuan Tang Nicholas Andrikopoulos Yuhuan Li Stone Ke Yunxiang Sun Feng Ding Pu Chun Ke |
| author_sort | Huayuan Tang |
| collection | DOAJ |
| description | Abstract The amyloid hypothesis has been a leading narrative concerning the pathophysiological foundation of Alzheimer’s and Parkinson’s disease. At the two ends of the hypothesis lie the functional protein monomers and the pathology-defining amyloid fibrils, while the early stages of protein aggregation are populated by polymorphic, transient and neurotoxic oligomers. As the structure and activity of oligomers are intertwined, here we show oligomers arising from liquid-liquid phase separation and β-barrel formation, their routes to neurodegeneration, and their role in cerebrovascular perturbation. Together, this Perspective converges on the multifaceted oligomer-axis central to the pathological origin and, hence, the treatment of amyloid diseases. |
| format | Article |
| id | doaj-art-fe5ea6d89d164d12ada7a161f909d641 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-fe5ea6d89d164d12ada7a161f909d6412025-08-20T02:49:27ZengNature PortfolioNature Communications2041-17232025-03-0116111310.1038/s41467-025-58335-yEmerging biophysical origins and pathogenic implications of amyloid oligomersHuayuan Tang0Nicholas Andrikopoulos1Yuhuan Li2Stone Ke3Yunxiang Sun4Feng Ding5Pu Chun Ke6Department of Engineering Mechanics, Hohai UniversityDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash UniversityDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash UniversityMelbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of MelbourneSchool of Physical Science and Technology, Ningbo UniversityDepartment of Physics and Astronomy, Clemson UniversityDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash UniversityAbstract The amyloid hypothesis has been a leading narrative concerning the pathophysiological foundation of Alzheimer’s and Parkinson’s disease. At the two ends of the hypothesis lie the functional protein monomers and the pathology-defining amyloid fibrils, while the early stages of protein aggregation are populated by polymorphic, transient and neurotoxic oligomers. As the structure and activity of oligomers are intertwined, here we show oligomers arising from liquid-liquid phase separation and β-barrel formation, their routes to neurodegeneration, and their role in cerebrovascular perturbation. Together, this Perspective converges on the multifaceted oligomer-axis central to the pathological origin and, hence, the treatment of amyloid diseases.https://doi.org/10.1038/s41467-025-58335-y |
| spellingShingle | Huayuan Tang Nicholas Andrikopoulos Yuhuan Li Stone Ke Yunxiang Sun Feng Ding Pu Chun Ke Emerging biophysical origins and pathogenic implications of amyloid oligomers Nature Communications |
| title | Emerging biophysical origins and pathogenic implications of amyloid oligomers |
| title_full | Emerging biophysical origins and pathogenic implications of amyloid oligomers |
| title_fullStr | Emerging biophysical origins and pathogenic implications of amyloid oligomers |
| title_full_unstemmed | Emerging biophysical origins and pathogenic implications of amyloid oligomers |
| title_short | Emerging biophysical origins and pathogenic implications of amyloid oligomers |
| title_sort | emerging biophysical origins and pathogenic implications of amyloid oligomers |
| url | https://doi.org/10.1038/s41467-025-58335-y |
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