Abstract:
BACKGROUND:Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System xc- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. METHODS:Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system xc-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT-/-) mice and irradiated mice reconstituted in xCT-/- bone marrow (BM), to their proper wild type (xCT+/+) controls. RESULTS:xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT+/+ mice, xCT-/- mice were equally susceptible to EAE, whereas mice transplanted with xCT-/- BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. CONCLUSIONS:Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system xc- on immune cells invading the CNS participates to EAE. Since a total loss of system xc- had no net beneficial effects, these results have important implications for targeting system xc- for treatment of MS.
journal_name
J Neuroinflammationjournal_title
Journal of neuroinflammationauthors
Merckx E,Albertini G,Paterka M,Jensen C,Albrecht P,Dietrich M,Van Liefferinge J,Bentea E,Verbruggen L,Demuyser T,Deneyer L,Lewerenz J,van Loo G,De Keyser J,Sato H,Maher P,Methner A,Massie Adoi
10.1186/s12974-016-0787-0subject
Has Abstractpub_date
2017-01-13 00:00:00pages
9issue
1issn
1742-2094pii
10.1186/s12974-016-0787-0journal_volume
14pub_type
杂志文章abstract:BACKGROUND:Multiple sclerosis (MS) is an immune-mediated demyelinated disease of the central nervous system. Activation of microglia is involved in the pathogenesis of myelin loss. OBJECTIVE:This study is focused on the role of Hv1 in regulating demyelination and microglial activation through reactive oxygen species (...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-02020-y
更新日期:2020-11-06 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
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更新日期:2016-08-30 00:00:00
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journal_title:Journal of neuroinflammation
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
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更新日期:2017-10-30 00:00:00
abstract:BACKGROUND:A key feature of the inflammatory response after cerebral ischemia is the brain infiltration of blood monocytes. There are two main monocyte subsets in the mouse blood: CCR2+Ly6Chi "inflammatory" monocytes involved in acute inflammation, and CX3CR1+Ly6Clo "patrolling" monocytes, which may play a role in repa...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
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更新日期:2016-11-04 00:00:00
abstract:BACKGROUND:Administration of exogenous interferon-γ (IFNγ) aggravates the symptoms of multiple sclerosis (MS), whereas interferon-β (IFNβ) is used for treatment of MS patients. We previously demonstrated that IFNγ induces apoptosis of oligodendroglial progenitor cells (OPCs), suggesting that IFNγ is more toxic to OPCs ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-8
更新日期:2011-01-24 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
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journal_title:Journal of neuroinflammation
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更新日期:2018-04-30 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
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更新日期:2017-02-20 00:00:00
abstract::Major depressive disorder (MDD) is a leading cause of disability worldwide. After the first episode, patients with remitted MDD have a 60% chance of experiencing a second episode. Consideration of therapy continuation should be viewed in terms of the balance between the adverse effects of medication and the need to pr...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章,评审
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更新日期:2019-04-17 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
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更新日期:2016-09-02 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
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更新日期:2019-06-29 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0381-x
更新日期:2015-10-06 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章,评审
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更新日期:2014-08-28 00:00:00
abstract:BACKGROUND:Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating and neurodegenerative diseases of the CNS. Although recent studies suggest the neuroprotective effects of oligodendrocytes in neurodegenerative diseases, it remains unknown whether ol...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1415-6
更新日期:2019-02-01 00:00:00
abstract:OBJECTIVES:The neurobiological basis for autism remains poorly understood. However, research suggests that environmentalfactors and neuroinflammation, as well as genetic factors, are contributors. This study aims to test the role that might be played by heat shock protein (HSP)70, transforming growth factor (TGF)-β2, C...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-9-265
更新日期:2012-12-11 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
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更新日期:2015-08-28 00:00:00
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pub_type: 杂志文章
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更新日期:2017-09-05 00:00:00
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journal_title:Journal of neuroinflammation
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journal_title:Journal of neuroinflammation
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更新日期:2013-10-29 00:00:00
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journal_title:Journal of neuroinflammation
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更新日期:2011-08-12 00:00:00
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journal_title:Journal of neuroinflammation
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更新日期:2020-02-12 00:00:00
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journal_title:Journal of neuroinflammation
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更新日期:2021-01-06 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
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更新日期:2019-03-30 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
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更新日期:2016-05-03 00:00:00
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更新日期:2020-10-15 00:00:00
abstract:BACKGROUND:Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of thiscascade. In the current study, we tested the hypothesis that curcumin, a phytochemical compound with po...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
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更新日期:2014-03-27 00:00:00
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journal_title:Journal of neuroinflammation
pub_type: 杂志文章
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更新日期:2015-10-26 00:00:00