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Abstract

The growing burden of chronic neurodegenerative diseases (NDs), particularly Parkinsons disease (PD), prompts the need for effective preventive strategies and treatments. Dietary (poly)phenols have emerged for their neuroprotective potential. This study investigated a (poly)phenol-enriched diet, comprising a berry mixture, to counteract key PD hallmarks in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice and elucidate the phenolic metabolic fingerprint underlying these effects. The berry-enriched diet prevented motor deficits in the MPTP mice model, preserved dopaminergic neurons in the midbrain, reduced glial activation and gene expression of inflammatory cytokines. Notably, berries also attenuated macrophage infiltration observed in the substantia nigra 7 days post-MPTP. Metabolomic analysis revealed distinct phenolic signatures in plasma and brain tissue between standard- and berry-fed mice. Overall, this pioneering study provides compelling evidence that a (poly)phenol-enriched diet may play a protective role in neurodegenerative disorders, highlighting its potential for future strategies to prevent or slow PD progression.

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