ArticleHuman molecular genetics2020
The mechanistic role of alpha-synuclein in the nucleus: impaired nuclear function caused by familial Parkinson's disease SNCA mutations.
Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 73 citations in OpenAlex.
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- In vivo Proximity & Spatial Proteomics with CRISPR Screening Identify STXBP1 as a Protective Modifier of α-synuclein Toxicity in Dopamine Neurons.bioRxiv : the preprint server for biology · 2026Article
- Organelle-Targeted Nanotherapeutics for Parkinson's Disease: From Pathogenesis to Preclinical Strategies and Translational Challenges.International journal of nanomedicine · 2026Review
- Early Amyloid Formation and Neuroinflammatory Response in a Bigenic Mouse Model Expressing Human α-Synuclein and Aβ.Parkinson's disease · 2026Article
- Revisiting the alpha-synuclein paradox in melanoma-Parkinson's disease connection: more than a tale of two cell fates.Cellular and molecular life sciences : CMLS · 2025Review
- Bridging the gap in Parkinson's disease research: from general pathophysiology to advanced 3d cell culture models.Cell communication and signaling : CCS · 2025Review
- Nanotechnology and CRISPR/Cas-Mediated Gene Therapy Strategies: Potential Role for Treating Genetic Disorders.Molecular biotechnology · 2025Review
- Pathological α-synuclein perturbs nuclear integrity.Neurobiology of disease · 2025Article
- Establishment and Characterization of Behavioral Changes in the Nuclear Localization Human α-Synuclein Transgenic Mice.Diseases (Basel, Switzerland) · 2025Article
- Glial reactivity and cognitive decline follow chronic heterochromatin loss in neurons.Nature communications · 2025Article
- Parkinson's Disease: Bridging Gaps, Building Biomarkers, and Reimagining Clinical Translation.Cells · 2025Review
- Pathological α-Synuclein Perturbs Nuclear Integrity.bioRxiv : the preprint server for biology · 2025Article
- Biological Amyloids Chemically Damage DNA.ACS chemical neuroscience · 2025Article
- Integrated Single-Cell and Spatial Transcriptomic Analysis Identifies ISR-Related Genes Driving Immune Regulation in Parkinson's Disease.Journal of inflammation research · 2025Article
- Ancient viral DNA in the human genome linked to neurodegenerative diseases.Brain, behavior, and immunity · 2025Article
- The Promise of Epigenetic Editing for Treating Brain Disorders.Sub-cellular biochemistry · 2025Review
- Recent advances in nanotechnology for Parkinson's disease: diagnosis, treatment, and future perspectives.Frontiers in medicine · 2025Review
- Adenosine diphosphate-ribosylation greatly affects proteins function: a focus on neurodegenerative diseases.Frontiers in aging neuroscience · 2025Review
- Alpha-synuclein null mutation exacerbates the phenotype of a model of Menkes disease in female mice.Frontiers in neuroscience · 2025Article
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9 authors at 1 institution in 1 country.
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Abstract
Alpha-synuclein SNCA has been implicated in the etiology of Parkinson's disease (PD); however, the normal function of alpha-synuclein protein and the pathway that mediates its pathogenic effect is yet to be discovered. We investigated the mechanistic role of SNCA in the nucleus utilizing isogenic human-induced pluripotent stem cells-derived neurons from PD patients with autosomal dominant mutations, A53T and SNCA-triplication, and their corresponding corrected lines by genome- and epigenome-editing. Comparisons of shape and integrity of the nuclear envelope and its resistance to stresses found that both mutations result in similar nuclear envelope perturbations that were reversed in the isogenic mutation-corrected cells. Further mechanistic studies showed that SNCA mutation has adverse effects on the nucleus by trapping Ras-related nuclear protein (RAN) and preventing it from transporting key nuclear proteins such as, DNMT3A, for maintaining normal nuclear function. For the first time, we proposed that α-syn interacts with RAN and normally functions in the nucleocytoplasmic transport while exerts its pathogenic effect by sequestering RAN. We suggest that defects in the nucleocytoplasmic transport components may be a general pathomechanistic driver of neurodegenerative diseases.
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