ArticleNature communications2019
Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson's disease pathogenesis.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers, 2 of them syntheses that pooled it.
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Who cites it
164 citing papers in PubMed, 2 syntheses or guidelines pooled it, 330 citations in OpenAlex.
- Potential Bioactive Function of Microbial Metabolites as Inhibitors of Tyrosinase: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Neuroinflammation in Parkinson's Disease: From Gene to Clinic: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Altered locus coeruleus links to atrophy and hypometabolism in individuals with high Alzheimer's disease biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Trial
- tris-Schiff Base Derivatives Containing Flurbiprofen as Potential Tyrosinase Inhibitors: Synthesis, In Vitro Evaluation, Molecular Docking, DFT and Dynamics Simulations.Chemistry & biodiversity · 2026Article
- Molecular programs in human locus coeruleus link APOE and neuromelanin to Alzheimer's vulnerability.Acta neuropathologica · 2026Article
- Rodent models and accompanying in vitro strategies for studying the etiology and therapy of Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Shared genetic architecture and neurobiological pathways of problematic alcohol use and anxiety disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Genetically Encoded Melanin as a Photostable Scattering Contrast for Whole-Brain Tomography.bioRxiv : the preprint server for biology · 2026Article
- Lactoperoxidase is a candidate for mediating neuromelanin formation in the human substantia nigra.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Bioprospecting Italian biodiversity for identifying potential neuroprotective agents.Scientific reports · 2026Article
- Neuroprotective and Renoprotective Potential of a Hydroethanolic Extract From the Aerial Parts of Mattiastrum paphlagonicum Bornm. (Boraginaceae).Chemistry & biodiversity · 2026Article
- Integrated LC-HRMS and HPLC Profiling of Fourteen AnatolianPharmaceuticals (Basel, Switzerland) · 2026Article
- Introducing PIGMO, a novel PIGmented MOuse model of Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Article
- Lignans inFrontiers in plant science · 2026Article
- Melanin and Neuromelanin in Humans: Insights Across Health, Aging, Diseases, and Unexpected Aspects of Fungal Melanogenesis.Biomolecules · 2025Review
- 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
- The Enigma of Neuromelanin: How Animal Models Can Help Researchers to Understand the Link Between Pigments and Neurodegeneration.Biomedicines · 2025Review
- Neuromelanin-induced cellular stress and neurotoxicity in the pathogenesis of Parkinson's disease.Apoptosis : an international journal on programmed cell death · 2025Review
- A Spatially Resolved View on the Aging Substantia nigra: An Exploratory Proteomic Study.Advanced biology · 2025Article
104 more citing papers are in PubMed but not listed here.
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16 authors at 6 institutions in 4 countries.
Funding
Abstract
In Parkinson's disease (PD) there is a selective degeneration of neuromelanin-containing neurons, especially substantia nigra dopaminergic neurons. In humans, neuromelanin accumulates with age, the latter being the main risk factor for PD. The contribution of neuromelanin to PD pathogenesis remains unknown because, unlike humans, common laboratory animals lack neuromelanin. Synthesis of peripheral melanins is mediated by tyrosinase, an enzyme also present at low levels in the brain. Here we report that overexpression of human tyrosinase in rat substantia nigra results in age-dependent production of human-like neuromelanin within nigral dopaminergic neurons, up to levels reached in elderly humans. In these animals, intracellular neuromelanin accumulation above a specific threshold is associated to an age-dependent PD phenotype, including hypokinesia, Lewy body-like formation and nigrostriatal neurodegeneration. Enhancing lysosomal proteostasis reduces intracellular neuromelanin and prevents neurodegeneration in tyrosinase-overexpressing animals. Our results suggest that intracellular neuromelanin levels may set the threshold for the initiation of PD.
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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.