ArticleBrain : a journal of neurology2023
In vivo reduction of age-dependent neuromelanin accumulation mitigates features of Parkinson's disease.
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 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- New insights into synaptic vesicle dysfunction in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- VMAT2 dysfunction impairs vesicular dopamine uptake, driving its oxidation and α-synuclein pathology in DJ-1-linked Parkinson's neurons.Science advances · 2026Article
- Introducing PIGMO, a novel PIGmented MOuse model of Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Molecular Mechanisms of Dopaminergic Neuron Degeneration in Parkinson's Disease: A Comprehensive Review.Current neuropharmacology · 2026Review
- 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
- LRRK2-mutant microglia and neuromelanin synergize to drive dopaminergic neurodegeneration in an iPSC-based Parkinson's disease model.Communications biology · 2025Article
- Phytochemicals in Parkinson's Disease: a Pathway to Neuroprotection and Personalized Medicine.Cell biochemistry and biophysics · 2025Review
- Induction of Ferroptotic Cell Death by Neuromelanin Pigments in Dopaminergic Cells.ACS chemical neuroscience · 2025Article
- Phytochemical Investigation ofPlants (Basel, Switzerland) · 2025Article
- Longitudinal neuromelanin changes in prodromal and early Parkinson's disease in humans and rat model.Brain communications · 2025Article
- Neuroprotective Effects of Dexamethasone in a Neuromelanin-Driven Parkinson's Disease Model.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Modelling human neuronal catecholaminergic pigmentation in rodents recapitulates age-related neurodegenerative deficits.Nature communications · 2024Article
- Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology.Neurotoxicology · 2024Review
- Neuroinflammation is linked to dementia risk in Parkinson's disease.Brain : a journal of neurology · 2024Article
- The specific NQO2 inhibitor, S29434, only marginally improves the survival of dopamine neurons in MPTP-intoxicated mice.Journal of neural transmission (Vienna, Austria : 1996) · 2024Article
- Neuromelanin accumulation drives endogenous synucleinopathy in non-human primates.Brain : a journal of neurology · 2023Article
- Role of dopamine in the pathophysiology of Parkinson's disease.Translational neurodegeneration · 2023Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Humans accumulate with age the dark-brown pigment neuromelanin inside specific neuronal groups. Neurons with the highest neuromelanin levels are particularly susceptible to degeneration in Parkinson's disease, especially dopaminergic neurons of the substantia nigra, the loss of which leads to characteristic motor Parkinson's disease symptoms. In contrast to humans, neuromelanin does not appear spontaneously in most animals, including rodents, and Parkinson's disease is an exclusively human condition. Using humanized neuromelanin-producing rodents, we recently found that neuromelanin can trigger Parkinson's disease pathology when accumulated above a specific pathogenic threshold. Here, by taking advantage of this newly developed animal model, we assessed whether the intracellular build-up of neuromelanin that occurs with age can be slowed down in vivo to prevent or attenuate Parkinson's disease. Because neuromelanin derives from the oxidation of free cytosolic dopamine, we enhanced dopamine vesicular encapsulation in the substantia nigra of neuromelanin-producing rats by viral vector-mediated overexpression of vesicular monoamine transporter 2 (VMAT2). This strategy reduced the formation of potentially toxic oxidized dopamine species that can convert into neuromelanin and maintained intracellular neuromelanin levels below their pathogenic threshold. Decreased neuromelanin production was associated with an attenuation of Lewy body-like inclusion formation and a long-term preservation of dopamine homeostasis, nigrostriatal neuronal integrity and motor function in these animals. Our results demonstrate the feasibility and therapeutic potential of modulating age-dependent intracellular neuromelanin production in vivo, thereby opening an unexplored path for the treatment of Parkinson's disease and, in a broader sense, brain ageing.
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