ArticleHuman molecular genetics2014
A calcineurin- and NFAT-dependent pathway is involved in α-synuclein-induced degeneration of midbrain dopaminergic neurons.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 86 citations in OpenAlex.
- Effects of Molecular Hydrogen Assessed by an Animal Model and a Randomized Clinical Study on Mild Cognitive Impairment.Current Alzheimer research · 2018Trial
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Identifying Immune Response Protein Biomarkers in Parkinson's-Related Cognitive Impairment and Depression.Molecular neurobiology · 2025Article
- Article
- Reduced Prevalence of Parkinson's Disease in Patients Prescribed Calcineurin Inhibitors.Journal of Parkinson's disease · 2024Article
- The alpha-synuclein oligomers activate nuclear factor of activated T-cell (NFAT) modulating synaptic homeostasis and apoptosis.Molecular medicine (Cambridge, Mass.) · 2023Article
- Tripartite Motif Protein Family in Central Nervous System Diseases.Cellular and molecular neurobiology · 2023Review
- Calcineurin inhibition protects against dopamine toxicity and attenuates behavioral decline in a Parkinson's disease model.Cell & bioscience · 2023Article
- Antagonistic effect of cyclin-dependent kinases and a calcium-dependent phosphatase on polyglutamine-expanded androgen receptor toxic gain of function.Science advances · 2023Article
- Trim39 regulates neuronal apoptosis by acting as a SUMO-targeted E3 ubiquitin-ligase for the transcription factor NFATc3.Cell death and differentiation · 2022Article
- Transcriptome deregulation of peripheral monocytes and whole blood in GBA-related Parkinson's disease.Molecular neurodegeneration · 2022Article
- Article
- Roles for α-Synuclein in Gene Expression.Genes · 2021Review
- Calcineurin Activity Is Increased in Charcot-Marie-Tooth 1B Demyelinating Neuropathy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Review
- Calmodulin and Its Binding Proteins in Parkinson's Disease.International journal of molecular sciences · 2021Review
- Isoform-Selective NFAT Inhibitor: Potential Usefulness and Development.International journal of molecular sciences · 2021Review
- Interaction between Parkin andCells · 2021Review
- NFATc3 inhibits hepatocarcinogenesis and HBV replication via positively regulating RIG-I-mediated interferon transcription.Oncoimmunology · 2021Article
- The Astrogenic Balance in the Aging Brain.Current neuropharmacology · 2021Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Parkinson's disease (PD), the most common degenerative movement disorder, is caused by a preferential loss of midbrain dopaminergic (mDA) neurons. Both α-synuclein (α-syn) missense and multiplication mutations have been linked to PD. However, the underlying intracellular signalling transduction pathways of α-syn-mediated mDA neurodegeneration remain elusive. Here, we show that transgenic expression of PD-related human α-syn A53T missense mutation promoted calcineurin (CN) activity and the subsequent nuclear translocation of nuclear factor of activated T cells (NFATs) in mDA neurons. α-syn enhanced the phosphatase activity of CN in both cell-free assays and cell lines transfected with either human wild-type or A53T α-syn. Furthermore, overexpression of α-syn A53T mutation significantly increased the CN-dependent nuclear import of NFATc3 in the mDA neurons of transgenic mice. More importantly, a pharmacological inhibition of CN by cyclosporine A (CsA) ameliorated the α-syn-induced loss of mDA neurons. These findings demonstrate an active involvement of CN- and NFAT-mediated signalling pathway in α-syn-mediated degeneration of mDA neurons in PD.
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Registered trials
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