Oxidative stress and inflammation in Parkinson's disease: is there a causal link?

Hald, Andreas; Lotharius, Julie

doi:10.1016/j.expneurol.2005.01.013

Cited by 459 publications

(343 citation statements)

References 126 publications

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“…NADPH oxidase and its protein subunits are mainly present in astrocytes and microglial cells (Serrano et al, 2003;Infanger et al, 2006;Takeya and Sumimoto, 2006). Several studies have provided evidence for the involvement of microglial NADPH oxidase in the inflammatory responses associated with the neurodegenerative process in MPTP-PD models (Beal, 2003;Serrano et al, 2003;Hald and Lotharius, 2005;Infanger et al, 2006;Sawada et al, 2006;Ushio-Fukai, 2006;Wersinger and Sidhu, 2006). Activated microglial cells exert quite different functions, including production of inflammatory cytokines, chemokines, and reactive superoxide ions.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, inflammation has also been suggested to contribute to the pathogenesis of PD (Beal, 2003;Hald and Lotharius, 2005;Sawada et al, 2006;Wersinger and Sidhu, 2006). ROS are among the inflammatory mediators capable of promoting neurodegeneration, which are derived from activation of microglial NADPH oxidase (Serrano et al, 2003;Infanger et al, 2006;Sawada et al, 2006;Ushio-Fukai, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Pharmacological inhibition of neuronal NADPH oxidase protects against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress and apoptosis in mesencephalic dopaminergic neuronal cells

et al. 2007

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Oxidative stress is widely recognized as a key mediator of degenerative processes in Parkinson's disease (PD). Recently, we demonstrated that the dopaminergic toxin MPP + initiates oxidative stress to cause caspase-3-dependent apoptotic cell death in mesencephalic dopaminergic neuronal (N27) cells. In this study, we determined the source of reactive oxygen species (ROS) produced during MPP + -induced apoptotic cell death. In addition to mitochondria, plasma membrane NADPH oxidase is considered a major producer of ROS inside the cell. Here, we show that N27 cells express key NADPH oxidase subunits gp91 phox and p67 phox . We used structurally diverse NADPH oxidase inhibitors, aminoethyl-benzenesulfonylfluoride (AEBSF, 100-1000 μM), apocynin (100-1000 μM), and diphenylene iodonium (DPI, 3-30 μM), to inhibit intrinsic NADPH oxidase activity in N27 cells. Flow cytometric analysis using the ROS-sensitive dye hydroethidine revealed that AEBSF blocked 300 μM MPP + -induced ROS production for over 45 min in N27 cells, in a dose-dependent manner. Further treatment with DPI, apocynin, and SOD also blocked MPP + -induced ROS production. In Sytox cell death assays, co-treatment with AEBSF, apocynin, or DPI for 24 hr significantly suppressed MPP + -induced cytotoxic cell death. Similarly, co-treatment with these inhibitors also significantly attenuated MPP + -induced increases in caspase-3 enzymatic activity. Furthermore, quantitative DNA fragmentation ELISA assays revealed that AEBSF, DPI, and apocynin rescue N27 cells from MPP + -induced apoptotic cell death. Together, these results indicate for the first time that intracellular ROS generated by NAPDH oxidase are present within the mesencephalic neuronal cells, and are a key determinant of MPP + -mediated dopaminergic degeneration in in vitro models of dopaminergic degeneration. This study supports a critical role of NADPH oxidase in the oxidative damage in PD; targeting this enzyme may lead to novel therapies for PD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacological inhibition of neuronal NADPH oxidase protects against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress and apoptosis in mesencephalic dopaminergic neuronal cells

et al. 2007

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“…Post-mortem examination of human subjects exposed to MPTP revealed the presence of activated microglia, decades after drug exposure, suggesting that even a brief pathogenic insult can induce an inflammatory response [8]. The iNOS expression was shown to be up-regulated in the substantia nigra of PD patients, but not of age-matched controls [9], suggesting that glial activation and the resulting release of NO may contribute to the chronic neurodegeneration that characterizes PD.…”

Section: Introductionmentioning

confidence: 94%

Minocycline exerts a neuroprotective action against 6-OHDA-induced neurotoxicity: in vivo and in vitro studies

Ferreira¹,

Viana²

2015

neurol neurosci

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Background: Parkinson's disease (PD) is a chronic neurological disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The oxidative stress and inflammation, among other factors, are involved in the mechanisms of cell death in PD. We studied the neuroprotective properties of minocycline (Mino), focusing on its behavioral, neurochemical and immunohistochemical effects. Besides, Mino effects were also studied on an in vitro model of PD, as well as on the release of MPO in human neutrophils, and also its antioxidant activity.

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“…Reactive oxygen species (ROS) mediated many of the pathophysiological events that cause several diseases including PD (Hald and Lotharius, 2005;Pong et al, 2001;Rastogi et al, 2006;Tamagno et al, 2003) and has been suggested to be involved in apoptotic cell death (Ahn et al, 2009). 6-OHDA administration results in the formation of ROS (Glinka et al, 1997).…”

Section: Transduction Of Tat-dj-1 Into Sh-sy5y Cellsmentioning

confidence: 99%

“…Prolonged exposure to ROS contributes significantly to the pathological processes of a number of human diseases and is a major factor in the cause of various neurodegenerative disorders including PD (Hald and Lotharius, 2005;Pong et al, 2001;Rastogi et al, 2006;Tamagno et al, 2003). In a previous study, we showed that the administration of a herbicide paraquat (1,1′-dimethy-4,4′-bipyridinium) triggers selective dopaminergic neuronal cell death and the exposure of mice to which is an effective model for studying the pathological aspects of PD (Choi et al, 2006a).…”

Section: Introductionmentioning

confidence: 99%

Transduced Tat-DJ-1 Protein Protects against Oxidative Stress-Induced SH-SY5Y Cell Death and Parkinson Disease in a Mouse Model

Jeong

Kim

Woo

et al. 2012

Molecules and Cells

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Parkinson's disease (PD) is a well known neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compact (SN). Although the exact mechanism remains unclear, oxidative stress plays a critical role in the pathogenesis of PD. DJ-1 is a multifunctional protein, a potent antioxidant and chaperone, the loss of function of which is linked to the autosomal recessive early onset of PD. Therefore, we investigated the protective effects of DJ-1 protein against SH-SY5Y cells and in a PD mouse model using a cell permeable Tat-DJ-1 protein. Tat-DJ-1 protein rapidly transduced into the cells and showed a protective effect on 6-hydroxydopamine (6-OHDA)-induced neuronal cell death by reducing the reactive oxygen species (ROS). In addition, we found that Tat-DJ-1 protein protects against dopaminergic neuronal cell death in 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP)-induced PD mouse models. These results suggest that Tat-DJ-1 protein provides a potential therapeutic strategy for against ROS related human diseases including PD.

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Oxidative stress and inflammation in Parkinson's disease: is there a causal link?

Cited by 459 publications

References 126 publications

Pharmacological inhibition of neuronal NADPH oxidase protects against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress and apoptosis in mesencephalic dopaminergic neuronal cells

Pharmacological inhibition of neuronal NADPH oxidase protects against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress and apoptosis in mesencephalic dopaminergic neuronal cells

Minocycline exerts a neuroprotective action against 6-OHDA-induced neurotoxicity: in vivo and in vitro studies

Transduced Tat-DJ-1 Protein Protects against Oxidative Stress-Induced SH-SY5Y Cell Death and Parkinson Disease in a Mouse Model

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