ArticleJournal of immunology (Baltimore, Md. : 1950)2008
Macrophage antigen complex-1 mediates reactive microgliosis and progressive dopaminergic neurodegeneration in the MPTP model of Parkinson's disease.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 2 of them syntheses that pooled it.
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Who cites it
79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 125 citations in OpenAlex.
- Neuroprotective Effects of Resveratrol in In vivo and In vitro Experimental Models of Parkinson's Disease: a Systematic Review.Neurotoxicity research · 2022Pooled it
- A systematic review of molecular approaches that link mitochondrial dysfunction and neuroinflammation in Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Pooled it
- Pharmacokinetics and pharmacodynamics of a single dose Nilotinib in individuals with Parkinson's disease.Pharmacology research & perspectives · 2019Trial
- Microglia-Neuron Crosstalk: An Intimate Molecular Conversation in Neurodegeneration.International journal of molecular sciences · 2026Review
- Identification and verification of key molecules in the epileptogenic process of focal cortical dysplasia.Metabolic brain disease · 2024Article
- Complement C3 Enhances LPS-Elicited Neuroinflammation and Neurodegeneration Via the Mac1/NOX2 Pathway.Molecular neurobiology · 2023Article
- Oral ellagic acid attenuated LPS-induced neuroinflammation in rat brain: MEK1 interaction and M2 microglial polarization.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Integrin Mac1 mediates paraquat and maneb-induced learning and memory impairments in mice through NADPH oxidase-NLRP3 inflammasome axis-dependent microglial activation.Journal of neuroinflammation · 2023Article
- Anti oxidative/neuro-inflammation properties ofBioinformation · 2023Article
- GSK-3β-mediated regulation of Nrf2/HO-1 signaling as a new therapeutic approach in the treatment of movement disorders.Pharmacological reports : PR · 2022Review
- Distinct phases of adult microglia proliferation: a Myc-mediated early phase and a Tnfaip3-mediated late phase.Cell discovery · 2022Article
- Review
- The CD200R1 microglial inhibitory receptor as a therapeutic target in the MPTP model of Parkinson's disease.Journal of neuroinflammation · 2021Article
- Dl-3-n-Butylphthalide Rescues Dopaminergic Neurons in Parkinson's Disease Models by Inhibiting the NLRP3 Inflammasome and Ameliorating Mitochondrial Impairment.Frontiers in immunology · 2021Article
- Nrf2/Wnt resilience orchestrates rejuvenation of glia-neuron dialogue in Parkinson's disease.Redox biology · 2020Review
- ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease.Antioxidants (Basel, Switzerland) · 2020Review
- Stress and brain immunity: Microglial homeostasis through hypothalamus-pituitary-adrenal gland axis and sympathetic nervous system.Brain, behavior, & immunity - health · 2020Review
- Glia-Derived Extracellular Vesicles in Parkinson's Disease.Journal of clinical medicine · 2020Review
- Nutraceuticals Targeting Generation and Oxidant Activity of Peroxynitrite May Aid Prevention and Control of Parkinson's Disease.International journal of molecular sciences · 2020Review
- Integrin CD11b mediates locus coeruleus noradrenergic neurodegeneration in a mouse Parkinson's disease model.Journal of neuroinflammation · 2020Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Neuronal death is known to trigger reactive microgliosis. However, little is known regarding the manner by which microglia are activated by injured neurons and how microgliosis participates in neurodegeneration. In this study we delineate the critical role of macrophage Ag complex-1 (MAC1), a member of the beta(2) integrin family, in mediating reactive microgliosis and promoting dopaminergic (DAergic) neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. MAC1 deficiency greatly attenuated the DAergic neurodegeneration induced by MPTP or 1-methyl-4-phenyl-pyridium iodide (MPP(+)) exposure both in vivo and in vitro, respectively. Reconstituted experiments created by adding microglia from MAC1(-/-) or MAC1(+/+) mice back to MAC1(+/+) neuron-enriched cultures showed that microglia with functional MAC1 expression was mandatory for microglia-enhanced neurotoxicity. Both in vivo and in vitro morphological and Western blot studies demonstrated that MPTP/MPP(+) produced less microglia activation in MAC1(-/-) mice than MAC1(+/+) mice. Further mechanistic studies revealed that a MPP(+)-mediated increase in superoxide production was reduced in MAC1(-/-) neuron-glia cultures compared with MAC1(+/+) cultures. The stunted production of superoxide in MAC1(-/-) microglia is likely linked to the lack of translocation of the cytosolic NADPH oxidase (PHOX) subunit (p47(phox)) to the membrane. In addition, the production of PGE(2) markedly decreased in neuron plus MAC1(-/-) microglia cocultures vs neuron plus MAC1(+/+) microglia cocultures. Taken together, these results demonstrate that MAC1 plays a critical role in MPTP/MPP(+)-induced reactive microgliosis and further support the hypothesis that reactive microgliosis is an essential step in the self-perpetuating cycle leading to progressive DAergic neurodegeneration observed in Parkinson's disease.
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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.