TY  - JOUR
AU  - Szegő, Éva M
AU  - Höfs, Lennart
AU  - Antoniou, Anna
AU  - Dinter, Elisabeth
AU  - Bernhardt, Nadine
AU  - Schneider, Anja
AU  - Di Monte, Donato A
AU  - Falkenburger, Björn
TI  - Intermittent fasting reduces alpha-synuclein pathology and functional decline in a mouse model of Parkinson's disease.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2025-00613
SP  - 4470
PY  - 2025
AB  - 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.
KW  - Animals
KW  - alpha-Synuclein: metabolism
KW  - alpha-Synuclein: genetics
KW  - Parkinson Disease: metabolism
KW  - Parkinson Disease: pathology
KW  - Parkinson Disease: therapy
KW  - Parkinson Disease: genetics
KW  - Fasting: physiology
KW  - Disease Models, Animal
KW  - Mice
KW  - Dopaminergic Neurons: metabolism
KW  - Dopaminergic Neurons: pathology
KW  - Male
KW  - Autophagy
KW  - Mice, Inbred C57BL
KW  - Dopamine: metabolism
KW  - Humans
KW  - Corpus Striatum: metabolism
KW  - Corpus Striatum: pathology
KW  - Microglia: metabolism
KW  - Intermittent Fasting
KW  - alpha-Synuclein (NLM Chemicals)
KW  - Dopamine (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40368903
DO  - DOI:10.1038/s41467-025-59249-5
UR  - https://pub.dzne.de/record/278657
ER  -