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Title:           Neuromelanin accumulation drives endogenous synucleinopathy in non-human primates
Subject:         DOI: 10.1093/brain/awad331; Brain, 146, 12, 2023-12-01.; 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, supportin
Keywords:        tyrosinase; alpha-synuclein; Lewy bodies; marinesco bodies; prion-like spread
Author:          Julia Chocarro
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     Item: 
      Title: Neuromelanin accumulation drives
endogenous synucleinopathy in non-human
primates
      Children: 
       Item: 
        Title: Introduction
        Destination: secawad331-s0
       Item: 
        Title: Materials and methods
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         Item: 
          Title: Study design
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         Item: 
          Title: Experimental animals
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         Item: 
          Title: Viral vector production
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         Item: 
          Title: Stereotaxic surgery for AAV deliveries
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         Item: 
          Title: Neuroimaging studies
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           Item: 
            Title: MicroPET scans
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           Item: 
            Title: MRI scans
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         Item: 
          Title: Necropsy, tissue processing and data analysis
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          Children: 
           Item: 
            Title: Quantification of pigmented SNpc neurons
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           Item: 
            Title: Quantification of neuromelanin intracellular levels
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           Item: 
            Title: Assessment of nigrostriatal degeneration
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           Item: 
            Title: Analysis of neuromelanin intracellular density and neuronal inclusions
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         Item: 
          Title: Quantification and statistical analysis
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       Item: 
        Title: Results
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         Item: 
          Title: Neuroimaging studies
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         Item: 
          Title: Neuromelanin accumulation induced by human tyrosinase gene overexpression
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         Item: 
          Title: Nigrostriatal neurodegeneration
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         Item: 
          Title: Intracellular aggregates
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          Title: Anterograde spread of endogenous α-synuclein
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          Title: Available NHP models of synucleinopathy
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         Item: 
          Title: Accuracy of the model in mimicking the known neuropathology of human Parkinson’s disease
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         Item: 
          Title: Anterograde spread of endogenous α-synuclein
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       Item: 
        Title: Conclusions
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       Item: 
        Title: Data availability
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        Title: Acknowledgements
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       Item: 
        Title: Funding
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        Title: Competing interests
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