ArticleiScience2020
α-Synuclein Translocates to the Nucleus to Activate Retinoic-Acid-Dependent Gene Transcription.
Article in iScience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 109 citations in OpenAlex.
- Alpha-Synuclein Dynamics in Cerebral Ischemia.ASN neuro · 2026Review
- Structural and functional insights into the nuclear role of Parkinson's disease-associated α-synuclein as a histone chaperone.Communications biology · 2025Article
- A novel function for α-synuclein as a regulator of NCK2 in olfactory bulb: implications for its role in olfaction.Cell & bioscience · 2024Article
- Systematic identification of structure-specific protein-protein interactions.Molecular systems biology · 2024Article
- Special Issue "Neurobiology of Protein Synuclein".International journal of molecular sciences · 2024Article
- Review
- α-Synuclein oligomers and fibrils: partners in crime in synucleinopathies.Neural regeneration research · 2023Article
- Changes in α-Synuclein Posttranslational Modifications in an AAV-Based Mouse Model of Parkinson's Disease.International journal of molecular sciences · 2023Article
- Reactive astrocytes targeting with oral vitamin A: Efficient neuronal regeneration for Parkinson's disease treatment and reversal of associated liver fibrosis.CNS neuroscience & therapeutics · 2023Article
- (Dys)functional insights into nucleic acids and RNA-binding proteins modulation of the prion protein and α-synuclein phase separation.Biophysical reviews · 2023Review
- Article
- Unraveling the Complex Interplay between Alpha-Synuclein and Epigenetic Modification.International journal of molecular sciences · 2023Review
- PPARs and Their Neuroprotective Effects in Parkinson's Disease: A Novel Therapeutic Approach in α-Synucleinopathy?International journal of molecular sciences · 2023Review
- Alpha-synuclein overexpression induces epigenomic dysregulation of glutamate signaling and locomotor pathways.Human molecular genetics · 2022Article
- Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity.NPJ Parkinson's disease · 2022Article
- Intestine-derived α-synuclein initiates and aggravates pathogenesis of Parkinson's disease in Drosophila.Translational neurodegeneration · 2022Article
- Nuclear alpha-synuclein is present in the human brain and is modified in dementia with Lewy bodies.Acta neuropathologica communications · 2022Article
- CK2 alpha prime and alpha-synuclein pathogenic functional interaction mediates synaptic dysregulation in huntington's disease.Acta neuropathologica communications · 2022Article
- Retinoid X Receptor: Cellular and Biochemical Roles of Nuclear Receptor with a Focus on Neuropathological Involvement.Molecular neurobiology · 2022Review
- α-Synuclein at the Presynaptic Axon Terminal as a Double-Edged Sword.Biomolecules · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
α-Synuclein (α-Syn) protein is implicated in the pathogenesis of Parkinson disease (PD). It is primarily cytosolic and interacts with cell membranes. α-Syn also occurs in the nucleus. Here we investigated the mechanisms involved in nuclear translocation of α-Syn. We analyzed alterations in gene expression following induced α-Syn expression in SH-SY5Y cells. Analysis of upstream regulators pointed at alterations in transcription activity of retinoic acid receptors (RARs) and additional nuclear receptors. We show that α-Syn binds RA and translocates to the nucleus to selectively enhance gene transcription. Nuclear translocation of α-Syn is regulated by calreticulin and is leptomycin-B independent. Importantly, nuclear translocation of α-Syn following RA treatment enhances its toxicity in cultured neurons and the expression levels of PD-associated genes, including ATPase cation transporting 13A2 (ATP13A2) and PTEN-induced kinase1 (PINK1). The results link a physiological role for α-Syn in the regulation of RA-mediated gene transcription and its toxicity in the synucleinopathies.
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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.