Intermittent fasting reduces alpha-synuclein pathology and functional decline in a mouse model of Parkinson’s disease

Éva M. Szegő (), Lennart Höfs, Anna Antoniou, Elisabeth Dinter, Nadine Bernhardt, Anja Schneider, Donato A. Monte and Björn H. Falkenburger ()
Additional contact information
Éva M. Szegő: TU Dresden
Lennart Höfs: TU Dresden
Anna Antoniou: University of Bonn
Elisabeth Dinter: TU Dresden
Nadine Bernhardt: TU Dresden
Anja Schneider: German Center for Neurodegenerative Diseases (DZNE)
Donato A. Monte: German Center for Neurodegenerative Diseases (DZNE)
Björn H. Falkenburger: TU Dresden

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron degeneration and α-synuclein (aSyn) accumulation. Environmental factors play a significant role in PD progression, highlighting the potential of non-pharmacological interventions. This study investigates the therapeutic effects of intermittent fasting (IF) in an rAAV-aSyn mouse model of PD. IF, initiated four weeks post-induction of aSyn pathology, improved motor function and reduced dopaminergic neuron and axon terminal degeneration. Additionally, IF preserved dopamine levels and synaptic integrity in the striatum. Mechanistically, IF enhanced autophagic activity, promoting phosphorylated-aSyn clearance and reducing its accumulation in insoluble brain fractions. Transcriptome analysis revealed IF-induced modulation of inflammation-related genes and microglial activation. Validation in primary cultures confirmed that autophagy activation and inflammatory modulators (CCL17, IL-36RN) mitigate aSyn pathology. These findings suggest that IF exerts neuroprotective effects, supporting further exploration of IF and IF-mimicking therapies as potential PD treatments.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-59249-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59249-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-59249-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().