Intermittent fasting reduces alpha-synuclein pathology and functional decline in a mouse model of Parkinson’s disease
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 invest...
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| Format: | Article |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59249-5 |
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| author | Éva M. Szegő Lennart Höfs Anna Antoniou Elisabeth Dinter Nadine Bernhardt Anja Schneider Donato A. Di Monte Björn H. Falkenburger |
| author_facet | Éva M. Szegő Lennart Höfs Anna Antoniou Elisabeth Dinter Nadine Bernhardt Anja Schneider Donato A. Di Monte Björn H. Falkenburger |
| author_sort | Éva M. Szegő |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e573d89c6af3435a9656129e83c5e758 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e573d89c6af3435a9656129e83c5e7582025-08-20T03:48:06ZengNature PortfolioNature Communications2041-17232025-05-0116112010.1038/s41467-025-59249-5Intermittent fasting reduces alpha-synuclein pathology and functional decline in a mouse model of Parkinson’s diseaseÉva M. Szegő0Lennart Höfs1Anna Antoniou2Elisabeth Dinter3Nadine Bernhardt4Anja Schneider5Donato A. Di Monte6Björn H. Falkenburger7Department of Neurology, TU DresdenDepartment of Neurology, TU DresdenDepartment of Old Age Psychiatry and Cognitive Disorders, University Hospital Bonn, University of BonnDepartment of Neurology, TU DresdenDepartment of Psychiatry and Psychotherapy, TU DresdenGerman Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)Department of Neurology, TU DresdenAbstract 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.https://doi.org/10.1038/s41467-025-59249-5 |
| spellingShingle | Éva M. Szegő Lennart Höfs Anna Antoniou Elisabeth Dinter Nadine Bernhardt Anja Schneider Donato A. Di Monte Björn H. Falkenburger Intermittent fasting reduces alpha-synuclein pathology and functional decline in a mouse model of Parkinson’s disease Nature Communications |
| title | Intermittent fasting reduces alpha-synuclein pathology and functional decline in a mouse model of Parkinson’s disease |
| title_full | Intermittent fasting reduces alpha-synuclein pathology and functional decline in a mouse model of Parkinson’s disease |
| title_fullStr | Intermittent fasting reduces alpha-synuclein pathology and functional decline in a mouse model of Parkinson’s disease |
| title_full_unstemmed | Intermittent fasting reduces alpha-synuclein pathology and functional decline in a mouse model of Parkinson’s disease |
| title_short | Intermittent fasting reduces alpha-synuclein pathology and functional decline in a mouse model of Parkinson’s disease |
| title_sort | intermittent fasting reduces alpha synuclein pathology and functional decline in a mouse model of parkinson s disease |
| url | https://doi.org/10.1038/s41467-025-59249-5 |
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