Spermine modulation of Alzheimer's Tau and Parkinson's α-synuclein: implications for biomolecular condensation and neurodegeneration.

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 expressing Tau and α-synuclein. Acting as a molecular glue,

SUBMITTER: Sun X 

PROVIDER: S-EPMC12639133 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature