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<p>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 <i>Perspective</i> converges on the multifaceted oligomer-axis central to the pathological origin and, hence, the treatment of amyloid diseases.</p>

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Emerging biophysical origins and pathogenic implications of amyloid oligomers

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月26日

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  • Huayuan Tang,
  • Nicholas Andrikopoulos,
  • Yuhuan Li,
  • Stone Ke,
  • Yunxiang Sun,
  • Feng Ding,
  • Pu Chun Ke

摘要

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.