Spermine modulation of Alzheimer’s Tau and Parkinson’s α-synuclein : implications for biomolecular condensation and neurodegeneration
(2025) In Nature Communications 16(1).- Abstract
Spermine, a pivotal player in biomolecular condensation and diverse cellular processes, has emerged as a focus of investigation in aging, neurodegeneration, and other diseases. Despite its significance, the mechanistic details of spermine remain incompletely understood. Here, we describe the distinct modulation by spermine on Alzheimer’s Tau and Parkinson’s α-synuclein, elucidating their condensation behaviors in vitro and in vivo. Using biophysical techniques including time-resolved SAXS and NMR, we trace electrostatically driven transitions from atomic-scale conformational changes to mesoscopic structures. Notably, spermine extends lifespan, ameliorates movement deficits, and restores mitochondrial function in C. elegans models... (More)
Spermine, a pivotal player in biomolecular condensation and diverse cellular processes, has emerged as a focus of investigation in aging, neurodegeneration, and other diseases. Despite its significance, the mechanistic details of spermine remain incompletely understood. Here, we describe the distinct modulation by spermine on Alzheimer’s Tau and Parkinson’s α-synuclein, elucidating their condensation behaviors in vitro and in vivo. Using biophysical techniques including time-resolved SAXS and NMR, we trace electrostatically driven transitions from atomic-scale conformational changes to mesoscopic structures. Notably, spermine extends lifespan, ameliorates movement deficits, and restores mitochondrial function in C. elegans models expressing Tau and α-synuclein. Acting as a molecular glue, spermine orchestrates in vivo condensation of α-synuclein, influences condensate mobility, and promotes degradation via autophagy, specifically through autophagosome expansion. This study unveils the interplay between spermine, protein condensation, and functional outcomes, advancing our understanding of neurodegenerative diseases and paving the way for therapeutic development.
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- author
- Sun, Xun ; Saha, Debasis ; Wang, Xue ; Mörman, Cecilia ; Sternke-Hoffmann, Rebecca ; Gerez, Juan Atilio ; Herranz, Fátima LU ; Riek, Roland ; Zheng, Wenwei and Luo, Jinghui
- organization
- publishing date
- 2025-12
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 16
- issue
- 1
- article number
- 10239
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:41271735
- scopus:105022661885
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-025-65426-3
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © The Author(s) 2025.
- id
- 2a511bc1-0730-41dc-976d-834076497603
- date added to LUP
- 2026-01-16 13:54:20
- date last changed
- 2026-01-30 15:14:43
@article{2a511bc1-0730-41dc-976d-834076497603,
abstract = {{<p>Spermine, a pivotal player in biomolecular condensation and diverse cellular processes, has emerged as a focus of investigation in aging, neurodegeneration, and other diseases. Despite its significance, the mechanistic details of spermine remain incompletely understood. Here, we describe the distinct modulation by spermine on Alzheimer’s Tau and Parkinson’s α-synuclein, elucidating their condensation behaviors in vitro and in vivo. Using biophysical techniques including time-resolved SAXS and NMR, we trace electrostatically driven transitions from atomic-scale conformational changes to mesoscopic structures. Notably, spermine extends lifespan, ameliorates movement deficits, and restores mitochondrial function in C. elegans models expressing Tau and α-synuclein. Acting as a molecular glue, spermine orchestrates in vivo condensation of α-synuclein, influences condensate mobility, and promotes degradation via autophagy, specifically through autophagosome expansion. This study unveils the interplay between spermine, protein condensation, and functional outcomes, advancing our understanding of neurodegenerative diseases and paving the way for therapeutic development.</p>}},
author = {{Sun, Xun and Saha, Debasis and Wang, Xue and Mörman, Cecilia and Sternke-Hoffmann, Rebecca and Gerez, Juan Atilio and Herranz, Fátima and Riek, Roland and Zheng, Wenwei and Luo, Jinghui}},
issn = {{2041-1723}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Nature Communications}},
title = {{Spermine modulation of Alzheimer’s Tau and Parkinson’s α-synuclein : implications for biomolecular condensation and neurodegeneration}},
url = {{http://dx.doi.org/10.1038/s41467-025-65426-3}},
doi = {{10.1038/s41467-025-65426-3}},
volume = {{16}},
year = {{2025}},
}