JNK inhibitor protects dopaminergic neurons by reducing COX-2 expression in the MPTP mouse model of subacute Parkinson's disease

Wang, Yongsheng; Zhang, Yuxin; Wei, Zifeng; Li, Hui; Zhou, Hongxia; Zhang, Zhiyong; Zhang, Zuo‐Feng

doi:10.1016/j.jns.2009.06.034

Cited by 36 publications

(16 citation statements)

References 36 publications

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“…cells in the SNc of mice in all the groups, just as previously described [11,29]. The sections that were used for counting covered the entire substantia nigra, and were analyzed for the total number of TH-i.p.…”

Section: Cell Countingmentioning

confidence: 99%

Tanshinone IIA prevents the loss of nigrostriatal dopaminergic neurons by inhibiting NADPH oxidase and iNOS in the MPTP model of Parkinson's disease

Ren

Zhang

Zhou

et al. 2015

Journal of the Neurological Sciences

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Section: Cell Countingmentioning

confidence: 99%

Tanshinone IIA prevents the loss of nigrostriatal dopaminergic neurons by inhibiting NADPH oxidase and iNOS in the MPTP model of Parkinson's disease

Ren

Zhang

Zhou

et al. 2015

Journal of the Neurological Sciences

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“…Genetic deletion of JNK2 and JNK3 protect against MPTP-induced neurodegeneration in mice (Hunot et al, 2004) and kinase inhibitors of JNK have neuroprotective effects in the MPTP (Saporito et al, 1999; Wang et al, 2004, 2009b; Chambers et al, 2011) and 6-OHDA (Chambers et al, 2013) models of PD. Moreover a host of anti-oxidant and anti-inflammatory compounds offering varying degrees of neuroprotection in these models are thought to have a mechanism of action, at least in part, involving inhibition of JNK activation (Xing et al, 2007; Castro-Caldas et al, 2012; Lee et al, 2013; Zhai et al, 2013).…”

Section: Kinases Experimentally Implicated In Pdmentioning

confidence: 99%

Parkinsonâ€™s disease-implicated kinases in the brain; insights into disease pathogenesis

Dzamko

Zhou

Huang

et al. 2014

Front. Mol. Neurosci.

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Substantial evidence implicates abnormal protein kinase function in various aspects of Parkinson’s disease (PD) etiology. Elevated phosphorylation of the PD-defining pathological protein, α-synuclein, correlates with its aggregation and toxic accumulation in neurons, whilst genetic missense mutations in the kinases PTEN-induced putative kinase 1 and leucine-rich repeat kinase 2, increase susceptibility to PD. Experimental evidence also links kinases of the phosphoinositide 3-kinase and mitogen-activated protein kinase signaling pathways, amongst others, to PD. Understanding how the levels or activities of these enzymes or their substrates change in brain tissue in relation to pathological states can provide insight into disease pathogenesis. Moreover, understanding when and where kinase dysfunction occurs is important as modulation of some of these signaling pathways can potentially lead to PD therapeutics. This review will summarize what is currently known in regard to the expression of these PD-implicated kinases in pathological human postmortem brain tissue.

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“…Indeed, several reports indicated that a JNK-mediated induction of COX-2 in neurons but not microglia is critical for DA neuron cytotoxicity following MPTP treatment [197, 198]. Moreover, Teismann and colleagues [176] provided compelling evidence favoring the importance of cell-autonomous oxidative processes (i.e., COX-2-derived ROS, DA-quinone formation) over PG-mediated inflammatory ones in COX-2-dependent neurodegeneration.…”

Section: Neuroinflammatory Mechanisms Of Pd: Microglia Cytokinesmentioning

confidence: 99%

Inflammatory Mechanisms of Neurodegeneration in Toxin-Based Models of Parkinson's Disease

Litteljohn

Mangano

Clarke

et al. 2011

Parkinson's Disease

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Parkinson's disease (PD) has been associated with exposure to a variety of environmental agents, including pesticides, heavy metals, and organic pollutants; and inflammatory processes appear to constitute a common mechanistic link among these insults. Indeed, toxin exposure has been repeatedly demonstrated to induce the release of oxidative and inflammatory factors from immunocompetent microglia, leading to damage and death of midbrain dopamine (DA) neurons. In particular, proinflammatory cytokines such as tumor necrosis factor-α and interferon-γ, which are produced locally within the brain by microglia, have been implicated in the loss of DA neurons in toxin-based models of PD; and mounting evidence suggests a contributory role of the inflammatory enzyme, cyclooxygenase-2. Likewise, immune-activating bacterial and viral agents were reported to have neurodegenerative effects themselves and to augment the deleterious impact of chemical toxins upon DA neurons. The present paper will focus upon the evidence linking microglia and their inflammatory processes to the death of DA neurons following toxin exposure. Particular attention will be devoted to the possibility that environmental toxins can activate microglia, resulting in these cells adopting a “sensitized” state that favors the production of proinflammatory cytokines and damaging oxidative radicals.

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JNK inhibitor protects dopaminergic neurons by reducing COX-2 expression in the MPTP mouse model of subacute Parkinson's disease

Cited by 36 publications

References 36 publications

Tanshinone IIA prevents the loss of nigrostriatal dopaminergic neurons by inhibiting NADPH oxidase and iNOS in the MPTP model of Parkinson's disease

Tanshinone IIA prevents the loss of nigrostriatal dopaminergic neurons by inhibiting NADPH oxidase and iNOS in the MPTP model of Parkinson's disease

Parkinsonâ€™s disease-implicated kinases in the brain; insights into disease pathogenesis

Inflammatory Mechanisms of Neurodegeneration in Toxin-Based Models of Parkinson's Disease

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