ArticlePloS one2016
Microglia-Derived Cytokines/Chemokines Are Involved in the Enhancement of LPS-Induced Loss of Nigrostriatal Dopaminergic Neurons in DJ-1 Knockout Mice.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 65 citations in OpenAlex.
- Neuronal DJ-1 regulates microglial activation in Parkinson's disease.Neural regeneration research · 2026Article
- LRRK2 kinase activity restricts NRF2-dependent mitochondrial protection in microglia.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Stable Dopamine-Signaling mRNA Co-Expression in the Substantia Nigra Is Deregulated in Pathological Conditions, but Not in Dopamine Transporter Knockout Rats.Biomolecules · 2025Article
- Neuroinflammation Based Neurodegenerative In Vitro Model of SH-SY5Y Cells-Differential Effects on Oxidative Stress and Insulin Resistance Relevant to Alzheimer's Pathology.International journal of molecular sciences · 2025Article
- Hypoxia-inducible factor-1 as targets for neuroprotection : from ferroptosis to Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Loss of DJ-1 alleviates microglia-mediated neuroinflammation in Parkinson's disease via autophagy-lysosomal degradation of NLRP3.Frontiers in immunology · 2025Article
- Tribuli Fructus alleviates 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease by suppressing neuroinflammation via JNK signaling.Metabolic brain disease · 2024Article
- Neuropsychiatric Burden of SARS-CoV-2: A Review of Its Physiopathology, Underlying Mechanisms, and Management Strategies.Viruses · 2024Review
- The immune system in Parkinson's disease: what we know so far.Brain : a journal of neurology · 2024Review
- Microglia: roles and genetic risk in Parkinson's disease.Frontiers in neuroscience · 2024Review
- Emerging Paradigms in Inflammatory Disease Management: Exploring Bioactive Compounds and the Gut Microbiota.Brain sciences · 2023Review
- The Endotoxin Hypothesis of Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2023Review
- Conserved and cell type-specific transcriptional responses to IFN-γ in the ventral midbrain.Brain, behavior, and immunity · 2023Article
- Microglia activation in the presence of intact blood-brain barrier and disruption of hippocampal neurogenesis via IL-6 and IL-18 mediate early diffuse neuropsychiatric lupus.Annals of the rheumatic diseases · 2023Article
- PARK7/DJ-1 in microglia: implications in Parkinson's disease and relevance as a therapeutic target.Journal of neuroinflammation · 2023Review
- Toll-like receptors 2 and 4 differentially regulate the self-renewal and differentiation of spinal cord neural precursor cells.Stem cell research & therapy · 2022Article
- Protective Signature of IFNγ-Stimulated Microglia Relies on miR-124-3p Regulation From the Secretome Released by Mutant APP Swedish Neuronal Cells.Frontiers in pharmacology · 2022Article
- Distinct Cell-specific Roles of NOX2 and MyD88 in Epileptogenesis.Frontiers in cell and developmental biology · 2022Review
- Gliotoxicity and Glioprotection: the Dual Role of Glial Cells.Molecular neurobiology · 2021Review
- Cytoprotective Mechanisms of DJ-1: Implications in Cardiac Pathophysiology.Molecules (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutation of DJ-1 (PARK7) has been linked to the development of early-onset Parkinson's disease (PD). However, the underlying molecular mechanism is still unclear. This study is aimed to compare the sensitivity of nigrostriatal dopaminergic neurons to lipopolysaccharide (LPS) challenge between DJ-1 knockout (KO) and wild-type (WT) mice, and explore the underlying cellular and molecular mechanisms. Our results found that the basal levels of interferon (IFN)-γ (the hub cytokine) and interferon-inducible T-cell alpha chemoattractant (I-TAC) (a downstream mediator) were elevated in the substantia nigra of DJ-1 KO mice and in microglia cells with DJ-1 deficiency, and the release of cytokine/chemokine was greatly enhanced following LPS administration in the DJ-1 deficient conditions. In addition, direct intranigral LPS challenge caused a greater loss of nigrostriatal dopaminergic neurons and striatal dopamine content in DJ-1 KO mice than in WT mice. Furthermore, the sensitization of microglia cells to LPS challenge to release IFN-γ and I-TAC was via the enhancement of NF-κB signaling, which was antagonized by NF-κB inhibitors. LPS-induced increase in neuronal death in the neuron-glia co-culture was enhanced by DJ-1 deficiency in microglia, which was antagonized by the neutralizing antibodies against IFN-γ or I-TAC. These results indicate that DJ-1 deficiency sensitizes microglia cells to release IFN-γ and I-TAC and causes inflammatory damage to dopaminergic neurons. The interaction between the genetic defect (i.e. DJ-1) and inflammatory factors (e.g. LPS) may contribute to the development of PD.
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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.