Induction of Glial Fibrillary Acidic Protein Expression in Astrocytes by Nitric Oxide

Brahmachari, Saurav; Fung, Yiu K.; Pahan, Kalipada

doi:10.1523/jneurosci.5480-05.2006

Cited by 314 publications

(254 citation statements)

References 41 publications

(54 reference statements)

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“…Markey et al (23) (25,26), which have been shown to play an important role in the loss of dopaminergic neurons in MPTPintoxicated mice and PD patients (8)(9)(10)(11)(12). Recently, we have demonstrated that, once NO is produced via NF-B-dependent pathway, it up-regulates the expression of GFAP in astroglia and the expression of CD11b in microglia through NF-B-independent but guanylate cyclase-cGMP-protein kinase G-dependent pathways (27,28). Because glial production of proinflammatory molecules and gliosis are important features of PD pathology, it appears that NF-B activation regulates these pathological features either directly or indirectly and that NBD peptide protects dopaminergic neurons in MPTP-intoxicated mice via suppression of NF-Bdependent pathological steps.…”

Section: Discussionmentioning

confidence: 99%

Selective inhibition of NF-κB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease

Ghosh

Roy

Liu

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

387

434

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Parkinson's disease (PD) is the second most common neurodegenerative disorder. Despite intense investigations, no effective therapy is available to stop its onset or halt its progression. The present study evaluates the ability of peptide corresponding to the NF-B essential modifier-binding domain (NBD) of I B kinase ␣ (IKK␣) or IKK␤ to prevent nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and establish a role for NF-B in human parkinsonism. First, we found that NF-B was activated within the substantia nigra pars compacta of PD patients and MPTP-intoxicated mice. However, i.p. injection of wild-type NBD peptide reduced nigral activation of NF-B, suppressed nigral microglial activation, protected both the nigrostriatal axis and neurotransmitters, and improved motor functions in MPTP-intoxicated mice. These findings were specific because mutated NBD peptide had no effect. We conclude that selective inhibition of NF-B activation by NBD peptide may be of therapeutic benefit for PD patients.MPTP ͉ NBD peptides ͉ neurodegeneration

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Section: Discussionmentioning

confidence: 99%

Selective inhibition of NF-κB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease

Ghosh

Roy

Liu

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

387

434

View full text Add to dashboard Cite

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“…Furthermore, the hypertrophy of GFAP-positive filaments has often been interpreted as evidence of cellular hypertrophy creating hostile environment for neurons (Brahmachari et al, 2006). Recently, these concepts are being re-evaluated due to the advancements of research tools and improved understanding of astrocyte physiology.…”

Section: Discussionmentioning

confidence: 99%

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Sikorska

Lanthier

Miller

et al. 2014

Neurobiology of Aging

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Although the support for the use of antioxidants, such as coenzyme Q 10 (CoQ 10 ), to treat Parkinson's disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ 10 is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ 10 (Ubisol-Q 10 ) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD. We used a subchronic MPTP model (5-daily MPTP injections), characterized by 50% loss of dopamine neurons over a period of 28 days. Ubisol-Q 10 was delivered in drinking water. Prophylactic application of Ubisol-Q 10 , started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q 10 group by day 28). Therapeutic application of Ubisol-Q 10 , given after the last MPTP injection, was equally effective. At the time of intervention on day 5 nearly 25% of dopamine neurons were already lost, but the treatment saved the remaining 25% of cells, which otherwise would have died by day 28. This was confirmed by cell counts, analyses of striatal dopamine levels, and improved animals' motor skill on a beam walk test. Similar levels of neuroprotection were obtained with 3 different Ubisol-Q 10 concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ 10 /kg body weight/day, showing clearly that high doses of CoQ 10 were not required to deliver these effects. Furthermore, the Ubisol-Q 10 treatments brought about a robust astrocytic activation in the brain parenchyma, indicating that astroglia played an active role in this neuroprotection. Thus, we have shown for the first time that Ubisol-Q 10 was capable of halting the neurodegeneration already in progress;

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“…It has been demonstrated that IFNg induces NO production and increases levels of GFAP in primary astrocytes. 31 Expression of SOD1 G93A or SOD1 G37R in astrocytes is accompanied by increased levels of ROS, including NO, 4,7 and expression of SOD1 G93A in glioblastoma leads to the production of IFNg. 32 How IFNg and ROS cooperate in the acquisition or the consolidation of the reactive status of astrocytes expressing SOD1 mutations remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

IFNγ triggers a LIGHT-dependent selective death of motoneurons contributing to the non-cell-autonomous effects of mutant SOD1

et al. 2010

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Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that primarily affects motoneurons in the brain and spinal cord. Dominant mutations in superoxide dismutase-1 (SOD1) cause a familial form of ALS. Mutant SOD1-damaged glial cells contribute to ALS pathogenesis by releasing neurotoxic factors, but the mechanistic basis of the motoneuron-specific elimination is poorly understood. Here, we describe a motoneuron-selective death pathway triggered by activation of lymphotoxin-b receptor (LT-bR) by LIGHT, and operating by a novel signaling scheme. We show that astrocytes expressing mutant SOD1 mediate the selective death of motoneurons through the proinflammatory cytokine interferon-c (IFNc), which activates the LIGHT-LT-bR death pathway. The expression of LIGHT and LT-bR by motoneurons in vivo correlates with the preferential expression of IFNc by motoneurons and astrocytes at disease onset and symptomatic stage in ALS mice. Importantly, the genetic ablation of Light in an ALS mouse model retards progression, but not onset, of the disease and increases lifespan. We propose that IFNc contributes to a cross-talk between motoneurons and astrocytes causing the selective loss of some motoneurons following activation of the LIGHT-induced death pathway.

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Induction of Glial Fibrillary Acidic Protein Expression in Astrocytes by Nitric Oxide

Cited by 314 publications

References 41 publications

Selective inhibition of NF-κB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease

Selective inhibition of NF-κB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

IFNγ triggers a LIGHT-dependent selective death of motoneurons contributing to the non-cell-autonomous effects of mutant SOD1

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