ArticleCell reports2022
Treadmill exercise reduces α-synuclein spreading via PPARα.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers, 4 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 4 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Effects of exercise on α-synuclein in rodent models of Parkinson's disease: a systematic review and meta-analysis.Experimental brain research · 2026Pooled it
- Current interventional model for movement in Parkinson's disease: network meta-analysis based on the improvement of motor ability.Frontiers in aging neuroscience · 2024Pooled it
- Parkinson's disease motor intervention patterns: a network meta-analysis based on patient motor function.Frontiers in neurology · 2024Pooled it
- Effects of exercise training on nigrostriatal neuroprotection in Parkinson's disease: a systematic review.Frontiers in neuroscience · 2024Pooled it
- Selective inhibition of TLR2 stimulates the maturation of oligodendroglial progenitor cells to oligodendrocytes.NeuroImmune pharmacology and therapeutics · 2026Article
- Site-targeted proximal complement C3 inhibition, but not C5 blockade, attenuates neurodegeneration in a mouse model of amyotrophic lateral sclerosis: Implications for failed clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Targeting GPCR Signaling in Parkinson's Disease: From Molecular Pathology to Exercise-Based Therapeutics.Molecular neurobiology · 2026Review
- Exercise Intervention for REM Sleep Behavior Disorder in Parkinson's Disease: Mechanisms and Implications for Neurorehabilitation.CNS neuroscience & therapeutics · 2026Review
- Neurobiology of exercise in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Corrected Version: Protection of Mice from Controlled Cortical Impact Injury by Food Additive Glyceryl Tribenzoate.Journal of clinical & experimental immunology · 2026Article
- Sex-specific effects of exercise on motor coordination and extended basal ganglia physiology.bioRxiv : the preprint server for biology · 2026Article
- L-Leucine Upregulates Lysosomal Biogenesis and Autophagy to Lower Plaques in 5XFAD Mouse Model of Alzheimer's Disease.Journal of neurochemistry · 2026Article
- HUWE1 in Skeletal Muscle Prevents Muscle Fatigue via Maintaining Iron and Calcium Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Enhancing effects of diphenyl diselenide and β-hydroxy β-methylbutyrate combined with exercise on neuroprotection, memory, mitochondrial function, muscle function, and inflammation regulation in older adults and age-related diseases.Frontiers in nutrition · 2026Review
- Corrected Version: Neutralization of RANTES and Eotaxin Prevents the Loss of Dopaminergic Neurons in a Mouse Model of Parkinson's Disease.Journal of clinical & experimental immunology · 2026Article
- Prospect of Muscle-Building Supplement HMB in Alzheimer's Disease.Journal of clinical & experimental immunology · 2026Article
- Intensive multidisciplinary rehabilitation modulates serumFrontiers in cellular neuroscience · 2026Article
- Systematic discovery of disease-modifying targets by prediction from knowledge graph-based AI model and experimental validation: Parkinson's disease case.Computational and structural biotechnology journal · 2026Article
- Unraveling the Function of PPARα in Neurodegenerative Disorders: A Potential Pathway to Novel Therapies.Biomedicines · 2025Review
- New perspectives on molecular mechanisms underlying exercise-induced benefits in Parkinson's disease.NPJ Parkinson's disease · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
This study underlines the importance of treadmill exercise in reducing α-synuclein (α-syn) spreading in the A53T brain and protecting nigral dopaminergic neurons. Preformed α-syn fibril (PFF) seeding in the internal capsule of young A53T α-syn mice leads to increased spreading of α-syn to substantia nigra and motor cortex and concomitant loss of nigral dopaminergic neurons. However, regular treadmill exercise decreases α-syn spreading in the brain and protects nigral dopaminergic neurons in PFF-seeded mice. Accordingly, treadmill exercise also mitigates α-synucleinopathy in aged A53T mice. While investigating this mechanism, we have observed that treadmill exercise induces the activation of peroxisome proliferator-activated receptor α (PPARα) in the brain to stimulate lysosomal biogenesis via TFEB. Accordingly, treadmill exercise remains unable to stimulate TFEB and reduce α-synucleinopathy in A53T mice lacking PPARα, and fenofibrate, a prototype PPARα agonist, reduces α-synucleinopathy. These results delineate a beneficial function of treadmill exercise in reducing α-syn spreading in the brain via PPARα.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.