ArticleThe Journal of biological chemistry2016
FTY720/Fingolimod Reduces Synucleinopathy and Improves Gut Motility in A53T Mice: CONTRIBUTIONS OF PRO-BRAIN-DERIVED NEUROTROPHIC FACTOR (PRO-BDNF) AND MATURE BDNF.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 70 citations in OpenAlex.
- Assessment of gastrointestinal function and enteric nervous system changes over time in the A53T mouse model of Parkinson's disease.Acta neuropathologica communications · 2025Article
- The Compelling Role of Brain-Derived Neurotrophic Factor Signaling in Multiple Sclerosis: Role of BDNF Activators.CNS neuroscience & therapeutics · 2024Review
- BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy.Journal of cellular and molecular medicine · 2024Review
- The Current Landscape in the Development of Small-molecule Modulators Targeting Sphingosine-1-phosphate Receptors to Treat Neurodegenerative Diseases.Current topics in medicinal chemistry · 2024Review
- Glycolipids in Parkinson's disease: beyond neuronal function.FEBS open bio · 2023Review
- Novel therapeutic targets to halt the progression of Parkinson's disease: an in-depth review on molecular signalling cascades.3 Biotech · 2023Review
- Molecular and neuroimmune pharmacology of S1P receptor modulators and other disease-modifying therapies for multiple sclerosis.Pharmacology & therapeutics · 2023Review
- Time- and Sex-Dependent Effects of Fingolimod Treatment in a Mouse Model of Alzheimer's Disease.Biomolecules · 2023Article
- Towards early detection of neurodegenerative diseases: A gut feeling.Frontiers in cell and developmental biology · 2023Review
- Antiparkinsonian Agents in Investigational Polymeric Micro- and Nano-Systems.Pharmaceutics · 2022Review
- Fingolimod increases parvalbumin-positive neurons in adult mice.IBRO neuroscience reports · 2022Article
- How Well Do Rodent Models of Parkinson's Disease Recapitulate Early Non-Motor Phenotypes? A Systematic Review.Biomedicines · 2022Review
- Therapeutics in the Pipeline TargetingPharmacological reviews · 2022Review
- Molecular Pharmacology and Novel Potential Therapeutic Applications of Fingolimod.Frontiers in pharmacology · 2022Review
- Evidence of Inflammation in Parkinson's Disease and Its Contribution to Synucleinopathy.Journal of movement disorders · 2022Article
- Repurposing Pomalidomide as a Neuroprotective Drug: Efficacy in an Alpha-Synuclein-Based Model of Parkinson's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Article
- Recent Insights into the Interplay of Alpha-Synuclein and Sphingolipid Signaling in Parkinson's Disease.International journal of molecular sciences · 2021Review
- Synucleinopathy-associated pathogenesis in Parkinson's disease and the potential for brain-derived neurotrophic factor.NPJ Parkinson's disease · 2021Review
- ATH434 Reverses Colorectal Dysfunction in the A53T Mouse Model of Parkinson's Disease.Journal of Parkinson's disease · 2021Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Patients with Parkinson's disease (PD) often have aggregated α-synuclein (aSyn) in enteric nervous system (ENS) neurons, which may be associated with the development of constipation. This occurs well before the onset of classic PD motor symptoms. We previously found that aging A53T transgenic (Tg) mice closely model PD-like ENS aSyn pathology, making them appropriate for testing potential PD therapies. Here we show that Tg mice overexpressing mutant human aSyn develop ENS pathology by 4 months. We then evaluated the responses of Tg mice and their WT littermates to the Food and Drug Administration-approved drug FTY720 (fingolimod, Gilenya) or vehicle control solution from 5 months of age. Long term oral FTY720 in Tg mice reduced ENS aSyn aggregation and constipation, enhanced gut motility, and increased levels of brain-derived neurotrophic factor (BDNF) but produced no significant change in WT littermates. A role for BDNF was directly assessed in a cohort of young A53T mice given vehicle, FTY720, the Trk-B receptor inhibitor ANA-12, or FTY720 + ANA-12 from 1 to 4 months of age. ANA-12-treated Tg mice developed more gut aSyn aggregation as well as constipation, whereas FTY720-treated Tg mice had reduced aSyn aggregation and less constipation, occurring in part by increasing both pro-BDNF and mature BDNF levels. The data from young and old Tg mice revealed FTY720-associated neuroprotection and reduced aSyn pathology, suggesting that FTY720 may also benefit PD patients and others with synucleinopathy. Another finding was a loss of tyrosine hydroxylase immunoreactivity in gut neurons with aggregated aSyn, comparable with our prior findings in the CNS.
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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.