Microglia and myeloperoxidase: A deadly partnership in neurodegenerative disease

Lefkowitz, Doris L.; Lefkowitz, Stanley S.

doi:10.1016/j.freeradbiomed.2008.05.021

Cited by 98 publications

(53 citation statements)

References 68 publications

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“…63,64 Upon activation by the ischemic insult, MPO generates highly reactive oxygen species and provides detrimental effects by inducing apoptosis, nitro-tyrosination of proteins and by enhancing the expression of pro-inflammatory cytokines. [65][66][67] Since MPO is abundantly found within the azurophilic granules of neutrophils, 68 its expression or activity has been extensively used to quantify neutrophil infiltration in the ischemic brain. 13,14,[69][70][71][72][73][74] Nevertheless, MPO activity assay is an indirect method and does not exclusively detect neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Properties of a Macrolide Antibiotic in a Mouse Model of Middle Cerebral Artery Occlusion: Characterization of the Immunomodulatory Effects and Validation of the Efficacy of Intravenous Administration

Amantea

Certo

Petrelli

et al. 2016

ASSAY and Drug Development Technologies

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Section: Discussionmentioning

confidence: 99%

Neuroprotective Properties of a Macrolide Antibiotic in a Mouse Model of Middle Cerebral Artery Occlusion: Characterization of the Immunomodulatory Effects and Validation of the Efficacy of Intravenous Administration

Amantea

Certo

Petrelli

et al. 2016

ASSAY and Drug Development Technologies

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“…Even basic science studies in rats have shown that MPO directly correlates with severity of myocardial infarction ( 15,16 ). Recently, immunochemical studies revealed that MPO is expressed in microglia, astrocytes, and certain types of neurons, suggesting that MPO could play an important role in neurodegenerative disease ( 17 ), such as multiple sclerosis (18)(19)(20), Alzheimer's ( 21,22 ), and Parkinson's disease ( 23 ). Interestingly, MPO has even been implicated as a risk factor for some forms of cancers ( 24,25 ).…”

Section: Mpo-mediated Ldl Malondialdehyde Formationmentioning

confidence: 99%

N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor

Zhang¹,

Jing²,

Shi³

et al. 2013

Journal of Lipid Research

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“…Activation and/or proliferation of astroglia and microglia is prominent during prion disease pathogenesis. Microglial and astroglial cells produce inflammatory mediators such as cytokines and chemokines in various neurodegenerative and infectious diseases, and all may contribute to the inflammation in prion disease (5,7,9,18,25,27,35). This neuroinflammatory reaction appears to be a host response to PrPres accumulation and associated brain cell damage.…”

mentioning

confidence: 99%

Early Cytokine Elevation, PrPres Deposition, and Gliosis in Mouse Scrapie: No Effect on Disease by Deletion of Cytokine Genes IL-12p40 and IL-12p35

Tribouillard-Tanvier

Race

Striebel

et al. 2012

J Virol

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Neurodegenerative diseases are typically associated with an activation of glia and an increased level of cytokines. In our previous studies of prion disease, the cytokine response in the brains of clinically sick scrapie-infected mice was restricted to a small group of cytokines, of which IL-12p40, CCL2, and CXCL10 were present at the highest levels. The goal of our current research was to determine the relationship between cytokine responses, gliosis, and neuropathology during prion disease. Here, in time course studies of C57BL/10 mice intracerebrally inoculated with 22L scrapie, abnormal protease-resistant prion protein (PrPres), astrogliosis, and microgliosis were first detected at 40 days after intracerebral scrapie inoculation. In cytokine studies, IL-12p40 was first elevated by 60 days; CCL3, IL-1␤, and CXCL1 were elevated by 80 days; and CCL2 and CCL5 were elevated by 115 days. IL12p40 showed the most extensive increase throughout disease and was 30-fold above control levels at the terminal stage. Because of the early onset and dramatic elevation of IL-12p40 during scrapie, we investigated whether IL-12p40 contributed to the development of prion disease neuropathogenesis by using three different scrapie strains (22L, RML, 79A) to infect knockout mice in which the gene encoding IL-12p40 was deleted. We also studied knockout mice lacking IL-12p35, which combines with IL-12p40 to form active IL-12 heterodimers. In all instances, knockout mice did not differ from control mice in survival time, clinical tempo, or levels of spongiosis, gliosis, or PrPres in the brain. Thus, neither IL-12p40 nor IL-12p35 molecules were required for prion disease-associated neurodegeneration or neuroinflammation. P rion diseases, also known as transmissible spongiform encephalopathy (TSE) diseases, are infectious neurodegenerative disorders that affect both humans and animals (24). Prion diseases are characterized by spongiform degeneration of gray matter, gliosis, and accumulation of a misfolded, partially protease resistant form, PrPres (also known as PrP Sc ), of the normal cellular prion protein, PrPsen (also known as PrP C ). Activation and/or proliferation of astroglia and microglia is prominent during prion disease pathogenesis. Microglial and astroglial cells produce inflammatory mediators such as cytokines and chemokines in various neurodegenerative and infectious diseases, and all may contribute to the inflammation in prion disease (5,7,9,18,25,27,35). This neuroinflammatory reaction appears to be a host response to PrPres accumulation and associated brain cell damage. However, this neuroinflammation might also act either to increase or to decrease prion disease pathogenesis, and if so, therapeutic intervention to increase or dampen this reaction might be beneficial.Our previous study focused on the cytokine response in vitro in glial cells and in vivo in the brains of sick mice after scrapie infection (35). Despite extensive gliosis during prion disease, scrapieinfected mice showed consistent significant elevation of ...

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Microglia and myeloperoxidase: A deadly partnership in neurodegenerative disease

Cited by 98 publications

References 68 publications

Neuroprotective Properties of a Macrolide Antibiotic in a Mouse Model of Middle Cerebral Artery Occlusion: Characterization of the Immunomodulatory Effects and Validation of the Efficacy of Intravenous Administration

Neuroprotective Properties of a Macrolide Antibiotic in a Mouse Model of Middle Cerebral Artery Occlusion: Characterization of the Immunomodulatory Effects and Validation of the Efficacy of Intravenous Administration

N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor

Early Cytokine Elevation, PrPres Deposition, and Gliosis in Mouse Scrapie: No Effect on Disease by Deletion of Cytokine Genes IL-12p40 and IL-12p35

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