ArticleAging cell2020
Attenuation of epigenetic regulator SMARCA4 and ERK-ETS signaling suppresses aging-related dopaminergic degeneration.
Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
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- Epigenetic regulation-mediated disorders in dopamine transporter endocytosis: A novel mechanism for the pathogenesis of Parkinson's disease.Theranostics · 2025Review
- Senescent Macrophages Release Inflammatory Cytokines and RNA-Loaded Extracellular Vesicles to Circumvent Fibroblast Senescence.Biomedicines · 2024Article
- Use-Dependent, Untapped Dual Kinase Signaling Localized in Brain Learning Circuitry.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- RNA-binding deficient TDP-43 drives cognitive decline in a mouse model of TDP-43 proteinopathy.eLife · 2023Article
- Unraveling the Complex Interplay between Alpha-Synuclein and Epigenetic Modification.International journal of molecular sciences · 2023Review
- Gene Set Enrichment Analysis and Genetic Experiment Reveal Changes in Cell Signaling Pathways Induced by α-Synuclein Overexpression.Biomedicines · 2023Article
- α-Synuclein and Mechanisms of Epigenetic Regulation.Brain sciences · 2023Review
- Epigenetic regulation of aging: implications for interventions of aging and diseases.Signal transduction and targeted therapy · 2022Review
- N6-methyladenosine and Neurological Diseases.Molecular neurobiology · 2022Review
- Roles of α-Synuclein and Disease-Associated Factors inInternational journal of molecular sciences · 2022Review
- Epigenetics of Aging and Aging-Associated Diseases.International journal of molecular sciences · 2021Review
- Attenuation of epigenetic regulator SMARCA4 and ERK-ETS signaling suppresses aging-related dopaminergic degeneration.Aging cell · 2020Article
Corrections and comments
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Authors and funding
24 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
How complex interactions of genetic, environmental factors and aging jointly contribute to dopaminergic degeneration in Parkinson's disease (PD) is largely unclear. Here, we applied frequent gene co-expression analysis on human patient substantia nigra-specific microarray datasets to identify potential novel disease-related genes. In vivo Drosophila studies validated two of 32 candidate genes, a chromatin-remodeling factor SMARCA4 and a biliverdin reductase BLVRA. Inhibition of SMARCA4 was able to prevent aging-dependent dopaminergic degeneration not only caused by overexpression of BLVRA but also in four most common Drosophila PD models. Furthermore, down-regulation of SMARCA4 specifically in the dopaminergic neurons prevented shortening of life span caused by α-synuclein and LRRK2. Mechanistically, aberrant SMARCA4 and BLVRA converged on elevated ERK-ETS activity, attenuation of which by either genetic or pharmacological manipulation effectively suppressed dopaminergic degeneration in Drosophila in vivo. Down-regulation of SMARCA4 or drug inhibition of MEK/ERK also mitigated mitochondrial defects in PINK1 (a PD-associated gene)-deficient human cells. Our findings underscore the important role of epigenetic regulators and implicate a common signaling axis for therapeutic intervention in normal aging and a broad range of age-related disorders including PD.
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