ArticleJournal of neuroinflammation2015
Neuromelanin activates proinflammatory microglia through a caspase-8-dependent mechanism.
Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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
29 citing papers in PubMed, 59 citations in OpenAlex.
- Rodent models and accompanying in vitro strategies for studying the etiology and therapy of Parkinson's disease.Journal of Parkinson's disease · 2026Review
- From Stress to Neurodegeneration: A New Look at the Pathogenesis of Parkinson's Disease.Biomedicines · 2026Review
- 3D imaging of neuronal inclusions and protein aggregates in human neurodegeneration by multiscale x-ray phase-contrast tomography.Brain pathology (Zurich, Switzerland) · 2026Article
- Melanin and Neuromelanin in Humans: Insights Across Health, Aging, Diseases, and Unexpected Aspects of Fungal Melanogenesis.Biomolecules · 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
- Induction of Ferroptotic Cell Death by Neuromelanin Pigments in Dopaminergic Cells.ACS chemical neuroscience · 2025Article
- Increased melanin induces aberrant keratinocyte - melanocyte - basal - fibroblast cell communication and fibrogenesis by inducing iron overload and ferroptosis resistance in keloids.Cell communication and signaling : CCS · 2025Article
- Effect of mRNA formulated with lipid nanoparticles on the transcriptomic and epigenetic profiles of F4/80Scientific reports · 2025Article
- ATF3 prevents retinal ganglion cell apoptosis and mitigates microglia-mediated neuroinflammation in retinal ischemia-reperfusion injury.Frontiers in immunology · 2025Article
- Caspase-8 in inflammatory diseases: a potential therapeutic target.Cellular & molecular biology letters · 2024Review
- Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology.Neurotoxicology · 2024Review
- OiScience · 2024Article
- Animal models of Parkinson's disease: bridging the gap between disease hallmarks and research questions.Translational neurodegeneration · 2023Review
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Immune Regulatory Functions of Macrophages and Microglia in Central Nervous System Diseases.International journal of molecular sciences · 2023Review
- Neuromelanins in brain aging and Parkinson's disease: synthesis, structure, neuroinflammatory, and neurodegenerative role.IUBMB life · 2023Article
- Article
- Neuromelanin-sensitive MRI correlates of cognitive and motor function in Parkinson's disease with freezing of gait.Frontiers in dementia · 2023Article
- Iron- and Neuromelanin-Weighted Neuroimaging to Study Mitochondrial Dysfunction in Patients with Parkinson's Disease.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe have uncovered a caspase-dependent (caspase-8/caspase-3/7) signaling governing microglia activation and associated neurotoxicity. Importantly, a profuse non-nuclear activation of cleaved caspases 8 and 3 was found in reactive microglia in the ventral mesencephalon from subjects with Parkinson's disease, thus supporting the existence of endogenous factors activating microglia through a caspase-dependent mechanism. One obvious candidate is neuromelanin, which is an efficient proinflammogen in vivo and in vitro and has been shown to have a role in the pathogenesis of Parkinson's disease. Consequently, the goal of this study is to test whether synthetic neuromelanin activates microglia in a caspase-dependent manner.
resultsWe found an in-vivo upregulation of CD16/32 (M1 marker) in Iba1-immunolabeled microglia in the ventral mesencephalon after neuromelanin injection. In vitro experiments using BV2 cells, a microglia-derived cell line, demonstrated that synthetic neuromelanin induced a significant chemotactic response to BV2 microglial cells, along with typical morphological features of microglia activation, increased oxidative stress and induction of pattern-recognition receptors including Toll-like receptor 2, NOD2, and CD14. Analysis of IETDase (caspase-8) and DEVDase (caspase-3/7) activities in BV2 cells demonstrated a modest but significant increase of both activities in response to neuromelanin treatment, in the absence of cell death.
conclusionsCaspase-8 inhibition prevented typical features of microglia activation, including morphological changes, a high rate of oxidative stress and expression of key proinflammatory cytokines and iNOS.
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Registered trials
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.