Hypothesis: Can N-acetylcysteine be beneficial in Parkinson's disease?

Martínez, Manuel Villanueva; Martı́nez, Natividad; Hernández, Ana Isabel; Ferrándiz, Marı́a Luisa

doi:10.1016/s0024-3205(98)00472-x

Cited by 58 publications

(39 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NAC is a thiol-reducing agent known to increase GSH pools and to react with ROS in cells (38,39). The present studies demonstrate that NAC attenuates the Cd 2ϩ effects on cytotoxicity, formation of HNE-protein adducts, COX-2 induction, and PGE2 production, as well as the decline in GSH, confirming that oxidative stress is an important mechanism mediating cadmium toxicity.…”

Section: Discussionsupporting

confidence: 75%

“…The demonstration that NAC decreases the HT4 neuronal cell loss in viability induced by 45 M Cd 2ϩ underscores the capability of the thiol-reducing agent to protect cells from oxidative stress. Because of their antioxidant properties, thiol-reducing agents such as NAC are emerging as potential therapeutic drugs to manage neurodegenerative disorders such as Parkinson's disease (38,39).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

N-Acetylcysteine and Celecoxib Lessen Cadmium Cytotoxicity Which Is Associated with Cyclooxygenase-2 Up-regulation in Mouse Neuronal Cells

Figueiredo‐Pereira

Jansen

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

In many neurodegenerative disorders, aggregates of ubiquitinated proteins are detected in neuronal inclusions, but their role in neurodegeneration remains to be defined. To identify intracellular mechanisms associated with the appearance of ubiquitin-protein aggregates, mouse neuronal HT4 cells were treated with cadmium. This heavy metal is a potent cell poison that mediates oxidative stress and disrupts the ubiquitin/ proteasome pathway. In the current studies, the following intracellular events were found to be also induced by cadmium: (i) a specific rise in cyclooxygenase-2 (COX-2) gene expression but not COX-1; (ii) an increase in the extracellular levels of the proinflammatory prostaglandin E2, a product of COX-2; and (iii) production of 4-hydroxy-2-nonenal-protein adducts, which result from lipid peroxidation. In addition, cadmium treatment led to the accumulation of high molecular weight ubiquitin-COX-2 conjugates and perturbed COX-2 glycosylation. The thiol-reducing antioxidant N-acetylcysteine, and, to a lesser extent, the COX-2 inhibitor celecoxib, attenuated the loss of cell viability induced by cadmium demonstrating that oxidative stress and COX-2 activation contribute to cadmium cytotoxicity. These findings establish that disruption of the ubiquitin/proteasome pathway is not the only event triggered by cadmium. This oxidative stressor also activates COX-2 function. Both events could be triggered by formation of 4-hydroxy-2-nonenal as a result of cadmium-induced lipid peroxidation. Proinflammatory responses stimulated by oxidative stressors that mimic the cadmium effects may, therefore, be important initiators of the neurodegenerative process and exacerbate its progress.

show abstract

Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

N-Acetylcysteine and Celecoxib Lessen Cadmium Cytotoxicity Which Is Associated with Cyclooxygenase-2 Up-regulation in Mouse Neuronal Cells

Figueiredo‐Pereira

Jansen

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Both directly (through catecholamine-and quinone-derived reactive oxygen species) and indirectly (through the formation of peroxynitrite), reactive oxygen species have been hypothesized to play a role in the sequelae of Parkinson's disease and its treatment with L-DOPA (Merad-Boudia et al, 1998;Spencer et al, 1998;Bonnet & Houeto, 1999;Han et al, 1999;Martinez et al, 1999; …”

Section: Discussionmentioning

confidence: 99%

The intracellular domain of p75NTR as a determinant of cellular reducing potential and response to oxidant stress

et al. 2005

View full text Add to dashboard Cite

SummaryThe low-affinity neurotrophin receptor, p75NTR, has been found to be pro-or anti-apoptotic depending upon the cell in which it is expressed. Reactive oxygen species play a major role in apoptosis induction and enactment. Using two polyclonal PC12 populations that, respectively, do or do not express p75NTR, this paper demonstrates that p75NTR expression confers resistance to oxidant stress upon PC12 cells maintained in serum-containing medium. The effect of p75NTR on cell survival is mimicked in p75-negative cells by expression of constructs that produce the p75NTR intracellular domain (ICD) or p75NTR with the extracellular domain deleted (∆ ∆ ∆ ∆ ECD), suggesting that binding of an extracellular ligand to p75NTR is not required. Our studies further document that the differential sensitivity to oxidant stress is serum-dependent and associated with differential oxidation of glutathione between p75-positive and p75-negative cells. These results suggest that the role of p75NTR in determining the consequences and treatment of age-related disorders and conditions in which reactive oxygen species are involved may require neither the extracellular receptor domain nor, by inference, the cognate extracellular ligands of this neurotrophin receptor.

show abstract

“…ROS formation and the oxidation of dopamine are thought to contribute to this process [80][81][82][83][84]. One study found that Tempol protected dopamine secreting cells in vitro from 6-hydroxydopamine (6-OHDA)-induced apoptosis [85].…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

The chemistry and biology of nitroxide compounds

Soule

Hyodo

Matsumoto

et al. 2007

Free Radical Biology and Medicine

467

387

View full text Add to dashboard Cite

Cyclic nitroxides are a diverse range of stable free radicals that have unique antioxidant properties. Because of their ability to interact with free radicals, they have been used for many years as biophysical tools. During the past 15-20 years, however, many interesting biochemical interactions have been discovered and harnessed for therapeutic applications. Biologically relevant effects of nitroxides have been described including their ability to degrade superoxide and peroxide, inhibit Fenton reactions and undergo radical-radical recombination. Cellular studies defined the activity of nitroxides in vitro. By modifying oxidative stress and altering the redox status of tissues, nitroxides have been found to interact with and alter many metabolic processes. These interactions can be exploited for therapeutic and research use including protection against ionizing radiation, as probes in functional magnetic resonance imaging, cancer prevention and treatment, control of hypertension and weight, and protection from damage resulting from ischemia/reperfusion injury. While much remains to be done, many applications have been well studied and some are presently being tested in clinical trials. The therapeutic and research uses of nitroxide compounds are reviewed here with a focus on the progress from initial development to modern trials.

show abstract

Hypothesis: Can N-acetylcysteine be beneficial in Parkinson's disease?

Cited by 58 publications

References 41 publications

N-Acetylcysteine and Celecoxib Lessen Cadmium Cytotoxicity Which Is Associated with Cyclooxygenase-2 Up-regulation in Mouse Neuronal Cells

N-Acetylcysteine and Celecoxib Lessen Cadmium Cytotoxicity Which Is Associated with Cyclooxygenase-2 Up-regulation in Mouse Neuronal Cells

The intracellular domain of p75NTR as a determinant of cellular reducing potential and response to oxidant stress

The chemistry and biology of nitroxide compounds

Contact Info

Product

Resources

About