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β-synuclein regulates the phase transitions and amyloid conversion of α-synuclein

Author

Listed:
  • Xi Li

    (Huazhong University of Science and Technology)

  • Linwei Yu

    (Huazhong University of Science and Technology)

  • Xikai Liu

    (Wuhan University)

  • Tianyi Shi

    (Huazhong University of Science and Technology)

  • Yu Zhang

    (Huazhong University of Science and Technology)

  • Yushuo Xiao

    (Huazhong University of Science and Technology)

  • Chen Wang

    (Huazhong University of Science and Technology)

  • Liangliang Song

    (Huazhong University of Science and Technology)

  • Ning Li

    (Huazhong University of Science and Technology)

  • Xinran Liu

    (Huazhong University of Science and Technology)

  • Yuchen Chen

    (Huazhong University of Science and Technology)

  • Robert B. Petersen

    (Central Michigan University College of Medicine)

  • Xiang Cheng

    (Huazhong University of Science and Technology)

  • Weikang Xue

    (Zhongnan Hospital of Wuhan University, Wuhan University)

  • Yanxun V. Yu

    (Zhongnan Hospital of Wuhan University, Wuhan University)

  • Li Xu

    (Huazhong University of Science and Technology)

  • Ling Zheng

    (Wuhan University)

  • Hong Chen

    (Huazhong University of Science and Technology)

  • Kun Huang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

Abstract

Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. β-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that β-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated β-synuclein mutations lose these capacities. Exogenous β-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated β-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/β-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and β-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials.

Suggested Citation

  • Xi Li & Linwei Yu & Xikai Liu & Tianyi Shi & Yu Zhang & Yushuo Xiao & Chen Wang & Liangliang Song & Ning Li & Xinran Liu & Yuchen Chen & Robert B. Petersen & Xiang Cheng & Weikang Xue & Yanxun V. Yu &, 2024. "β-synuclein regulates the phase transitions and amyloid conversion of α-synuclein," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53086-8
    DOI: 10.1038/s41467-024-53086-8
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    References listed on IDEAS

    as
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