ArticleEnvironmental health perspectives2008
Formyl-methionyl-leucyl-phenylalanine-induced dopaminergic neurotoxicity via microglial activation: a mediator between peripheral infection and neurodegeneration?
Article in Environmental health perspectives, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- Novel Non-Invasive PET Imaging of Reactive Oxygen Species Using [18 F]ROStrace in Three Proteinopathy-Associated Neurodegenerative Mouse Models.Academic radiology · 2026Article
- Potential Mechanisms Underlying COVID-19-Mediated Central and Peripheral Demyelination: Roles of the RAAS and ADAM-17.Molecular neurobiology · 2025Review
- PET Imaging with [Antioxidants (Basel, Switzerland) · 2024Article
- Natural Compounds Oridonin and Shikonin Exhibit Potentially Beneficial Regulatory Effects on Select Functions of Microglia.Brain sciences · 2024Article
- Involvement of microglial P2X7 receptor in pain modulation.CNS neuroscience & therapeutics · 2024Review
- Article
- Development of An Oral Treatment with the PPAR-γ-Acting Cannabinoid VCE-003.2 Against the Inflammation-Driven Neuronal Deterioration in Experimental Parkinson's Disease.Molecules (Basel, Switzerland) · 2019Article
- Formyl-methionyl-leucyl-phenylalanine Induces Apoptosis in Murine Neurons: Evidence for NO-Dependent Caspase-9 Activation.Biology · 2019Article
- Benefits of VCE-003.2, a cannabigerol quinone derivative, against inflammation-driven neuronal deterioration in experimental Parkinson's disease: possible involvement of different binding sites at the PPARγ receptor.Journal of neuroinflammation · 2018Article
- TGF-β1 Neuroprotection via Inhibition of Microglial Activation in a Rat Model of Parkinson's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017Article
- Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson's disease.Journal of neuroinflammation · 2017Article
- Mitochondria-Derived Damage-Associated Molecular Patterns in Neurodegeneration.Frontiers in immunology · 2017Review
- Immune-mediated processes in neurodegeneration: where do we stand?Journal of neurology · 2016Review
- Crosstalk between insulin-like growth factor-1 and angiotensin-II in dopaminergic neurons and glial cells: role in neuroinflammation and aging.Oncotarget · 2016Article
- Clozapine metabolites protect dopaminergic neurons through inhibition of microglial NADPH oxidase.Journal of neuroinflammation · 2016Article
- Mitochondrial lysates induce inflammation and Alzheimer's disease-relevant changes in microglial and neuronal cells.Journal of Alzheimer's disease : JAD · 2015Article
- Substance P exacerbates dopaminergic neurodegeneration through neurokinin-1 receptor-independent activation of microglial NADPH oxidase.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Bioenergetic dysfunction and inflammation in Alzheimer's disease: a possible connection.Frontiers in aging neuroscience · 2014Review
- Oral treatment with the NADPH oxidase antagonist apocynin mitigates clinical and pathological features of parkinsonism in the MPTP marmoset model.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2013Article
- Targeting microglia-mediated neurotoxicity: the potential of NOX2 inhibitors.Cellular and molecular life sciences : CMLS · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundParkinson disease (PD), a chronic neurodegenerative disease, has been proposed to be a multifactorial disorder resulting from a combination of environmental mechanisms (chemical, infectious, and traumatic), aging, and genetic deficits. Microglial activation is important in the pathogenesis of PD.
objectivesWe investigated dopaminergic (DA) neurotoxicity and the underlying mechanisms of formyl-methionyl-leucyl-phenylalanine (fMLP), a bacteria-derived peptide, in relation to PD.
methodsWe measured DA neurotoxicity using a DA uptake assay and immunocytochemical staining (ICC) in primary mesencephalic cultures from rodents. Microglial activation was observed via ICC, flow cytometry, and superoxide measurement.
resultsfMLP can cause selective DA neuronal loss at concentrations as low as 10(-13) M. Further, fMLP (10(-13) M) led to a significant reduction in DA uptake capacity in neuron/glia (N/G) cultures, but not in microglia-depleted cultures, indicating an indispensable role of microglia in fMLP-induced neurotoxicity. Using ICC of a specific microglial marker, OX42, we observed morphologic changes in activated microglia after fMLP treatment. Microglial activation after fMLP treatment was confirmed by flow cytometry analysis of major histocompatibility antigen class II expression on a microglia HAPI cell line. Mechanistic studies revealed that fMLP (10(-13) M)-induced increase in the production of extracellular superoxide from microglia is critical in mediating fMLP-elicited neurotoxicity. Pharmacologic inhibition of NADPH oxidase (PHOX) with diphenylene-iodonium or apocynin abolished the DA neurotoxicity of fMLP. N/G cultures from PHOX-deficient (gp91PHOX-/ -) mice were also insensitive to fMLP-induced DA neurotoxicity.
conclusionfMLP (10(-13) M) induces DA neurotoxicity through activation of microglial PHOX and subsequent production of superoxide, suggesting a role of fMLP in the central nervous system inflammatory process.
Indexed as
Identifiers
What OpenQuestion holds
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.