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...

Full description

Saved in:
Bibliographic Details
Main Authors: Huayuan Tang, Nicholas Andrikopoulos, Yuhuan Li, Stone Ke, Yunxiang Sun, Feng Ding, Pu Chun Ke
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58335-y
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850063908911448064
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
work_keys_str_mv AT huayuantang emergingbiophysicaloriginsandpathogenicimplicationsofamyloidoligomers
AT nicholasandrikopoulos emergingbiophysicaloriginsandpathogenicimplicationsofamyloidoligomers
AT yuhuanli emergingbiophysicaloriginsandpathogenicimplicationsofamyloidoligomers
AT stoneke emergingbiophysicaloriginsandpathogenicimplicationsofamyloidoligomers
AT yunxiangsun emergingbiophysicaloriginsandpathogenicimplicationsofamyloidoligomers
AT fengding emergingbiophysicaloriginsandpathogenicimplicationsofamyloidoligomers
AT puchunke emergingbiophysicaloriginsandpathogenicimplicationsofamyloidoligomers