ArticleBrain : a journal of neurology2023
Neuromelanin accumulation drives endogenous synucleinopathy in non-human primates.
Article in Brain : a journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 27 citations in OpenAlex.
- The MacBrain Resource Center (MBRC) rhesus macaque postnatal brain histology datasets: Enabling new discoveries through NHP tissue and digital data Repositories.Journal of anatomy · 2026Article
- When Pathways Converge: Iron, Lipid Peroxidation, and α-Synuclein in Ferroptosis-Driven Dopaminergic Neurodegeneration.Journal of neurochemistry · 2026Review
- Introducing PIGMO, a novel PIGmented MOuse model of Parkinson's disease.NPJ 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
- 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
- LRRK2-mutant microglia and neuromelanin synergize to drive dopaminergic neurodegeneration in an iPSC-based Parkinson's disease model.Communications biology · 2025Article
- Position paper: leveraging non-human primate (NHP) specificities to accelerate Parkinson's disease and ageing research.NPJ Parkinson's disease · 2025Review
- Longitudinal neuromelanin changes in prodromal and early Parkinson's disease in humans and rat model.Brain communications · 2025Article
- From pathogenesis to treatment: the emerging role of ferroptosis in Parkinson's disease.Frontiers in immunology · 2025Review
- Genetically modified E. Coli secreting melanin (E.melanin) activates the astrocytic PSAP-GPR37L1 pathway and mitigates the pathogenesis of Parkinson's disease.Journal of nanobiotechnology · 2024Article
- Investigation in the cannabigerol derivative VCE-003.2 as a disease-modifying agent in a mouse model of experimental synucleinopathy.Behavioral and brain functions : BBF · 2024Article
- New Aspects Regarding the Fluorescence Spectra of Melanin and Neuromelanin in Pigmented Human Tissue Concerning Hypoxia.International journal of molecular sciences · 2024Article
- The Skin-Brain Axis: From UV and Pigmentation to Behaviour Modulation.International journal of molecular sciences · 2024Review
- Development and characterization of a non-human primate model of disseminated synucleinopathy.Frontiers in neuroanatomy · 2024Article
- Neuromelanin as a nidus for neurodegeneration.Brain : a journal of neurology · 2023Article
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12 authors at 5 institutions in 2 countries.
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Abstract
Although neuromelanin is a dark pigment characteristic of dopaminergic neurons in the human substantia nigra pars compacta, its potential role in the pathogenesis of Parkinson's disease (PD) has often been neglected since most commonly used laboratory animals lack neuromelanin. Here we took advantage of adeno-associated viral vectors encoding the human tyrosinase gene for triggering a time-dependent neuromelanin accumulation within substantia nigra pars compacta dopaminergic neurons in macaques up to similar levels of pigmentation as observed in elderly humans. Furthermore, neuromelanin accumulation induced an endogenous synucleinopathy mimicking intracellular inclusions typically observed in PD together with a progressive degeneration of neuromelanin-expressing dopaminergic neurons. Moreover, Lewy body-like intracellular inclusions were observed in cortical areas of the frontal lobe receiving dopaminergic innervation, supporting a circuit-specific anterograde spread of endogenous synucleinopathy by permissive trans-synaptic templating. In summary, the conducted strategy resulted in the development and characterization of a new macaque model of PD matching the known neuropathology of this disorder with unprecedented accuracy. Most importantly, evidence is provided showing that intracellular aggregation of endogenous α-synuclein is triggered by neuromelanin accumulation, therefore any therapeutic approach intended to decrease neuromelanin levels may provide appealing choices for the successful implementation of novel PD therapeutics.
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