ArticlePloS one2012
The role of alpha-synuclein in melanin synthesis in melanoma and dopaminergic neuronal cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Cutaneous α-Synuclein and Age Spots in Neurodegeneration: A Systematic Review and Testable Hypothesis.International journal of molecular sciences · 2025Pooled it
- Malignant melanoma in early-treated Parkinson's disease: the NET-PD trial.Movement disorders : official journal of the Movement Disorder Society · 2014Trial
- Levodopa and Melanoma: Practical Recommendations for Parkinson's Disease-International Parkinson and Movement Disorder Society Scientific Issues Committee Viewpoint.Movement disorders clinical practice · 2026Article
- Article
- A Pathophysiological Model of Parkinson's Disease Based on Microvascular Flow Disturbance and Leukocyte-Mediated Oxidative Injury in Critical Pigmented Neuronal Niches.Antioxidants (Basel, Switzerland) · 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
- Neuromelanin-induced cellular stress and neurotoxicity in the pathogenesis of Parkinson's disease.Apoptosis : an international journal on programmed cell death · 2025Review
- Exploring the skin as an open window onto neurodegenerative diseases.Translational neurodegeneration · 2025Review
- Alpha-synuclein modulates the positioning of endolysosomes in melanoma cells.Human molecular genetics · 2025Article
- Link between Parkinson's disease and melanoma: insights into the influence of theFrontiers in oncology · 2025Review
- Transcriptomic analysis of melanoma cells reveals an association of α-synuclein with regulation of the inflammatory response.Scientific reports · 2024Article
- New Aspects Regarding the Fluorescence Spectra of Melanin and Neuromelanin in Pigmented Human Tissue Concerning Hypoxia.International journal of molecular sciences · 2024Article
- Impacts of gait freeze on quality of life in Parkinson's disease, from the perspectives of patients and their carers.Irish journal of medical science · 2024Article
- Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology.Neurotoxicology · 2024Review
- Large-scale functional network connectivity mediates the association between nigral neuromelanin hypopigmentation and motor impairment in Parkinson's disease.Brain structure & function · 2024Article
- Association between Parkinson's Disease and Cancer: New Findings and Possible Mediators.International journal of molecular sciences · 2024Review
- Generation and characterization of retinal pigment epithelium from patient iPSC line to model oculocutaneous albinism (OCA)1A disease.Journal of biosciences · 2024Article
- Neuromelanin accumulation drives endogenous synucleinopathy in non-human primates.Brain : a journal of neurology · 2023Article
- Double Trouble: Association of Malignant Melanoma with Sporadic and Genetic Forms of Parkinson's Disease and Asymptomatic Carriers of Related Genes: A Brief Report.Medicina (Kaunas, Lithuania) · 2023Article
- UVA/UVB Irradiation Exerts a Distinct Phototoxic Effect on Human Keratinocytes Compared to Human Malignant Melanoma Cells.Life (Basel, Switzerland) · 2023Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The relatively high co-occurrence of Parkinson's disease (PD) and melanoma has been established by a large number of epidemiological studies. However, a clear biological explanation for this finding is still lacking. Ultra-violet radiation (UVR)-induced skin melanin synthesis is a defense mechanism against UVR-induced damage relevant to the initiation of melanoma, whereas, increased neuromelanin (NM), the melanin synthesized in dopaminergic neurons, may enhance the susceptibility to oxidative stress-induced neuronal injury relevant to PD. SNCA is a PD-causing gene coding for alpha-Synuclein (α-Syn) that expresses not only in brain, but also in skin as well as in tumors, such as melanoma. The findings that α-Syn can interact with tyrosinase (TYR) and inhibit tyrosine hydroxylase (TH), both of which are enzymes involved in the biosynthesis of melanin and dopamine (DA), led us to propose that α-Syn may participate in the regulation of melanin synthesis. In this study, by applying ultraviolet B (UVB) light, a physiologically relevant stimulus of melanogenesis, we detected melanin synthesis in A375 and SK-MEL-28 melanoma cells and in SH-SY5Y and PC12 dopaminergic neuronal cells and determined effects of α-Syn on melanin synthesis. Our results showed that UVB light exposure increased melanin synthesis in all 4 cell lines. However, we found that α-Syn expression reduced UVB light-induced increase of melanin synthesis and that melanin content was lower when melanoma cells were expressed with α-Syn, indicating that α-Syn may have inhibitory effects on melanin synthesis in melanoma cells. Different from melanoma cells, the melanin content was higher in α-Syn-over-expressed dopaminergic neuronal SH-SY5Y and PC12 cells, cellular models of PD, than that in non-α-Syn-expressed control cells. We concluded that α-Syn could be one of the points responsible for the positive association between PD and melanoma via its differential roles in melanin synthesis in melanoma cells and in dopaminergic neuronal cells.
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