Quinone and oxyradical scavenging properties of N-acetylcysteine prevent dopamine mediated inhibition of Na+, K+-ATPase and mitochondrial electron transport chain activity in rat brain: implications in the neuroprotective therapy of Parkinson's disease.Bagh MB, Maiti AK, Jana S, Banerjee K, Roy A, Chakrabarti S.
SourceDepartment of Biochemistry, Institute of Post Graduate Medical Education & Research, Dr B. C. Roy Post Graduate Institute of Basic Medical Sciences, India.

Abstract
Dopamine oxidation products such as H2O2 and reactive quinones have been held responsible for various toxic actions of dopamine, which have implications in the aetiopathogenesis of Parkinson's disease. This study has shown that N-acetylcysteine (0.25-1 mm) is a potent scavenger of both H2O2 and toxic quinones derived from dopamine and it further prevents dopamine mediated inhibition of Na+,K+-ATPase activity and mitochondrial respiratory chain function. The quinone scavenging ability of N-acetylcysteine is presumably related to its protective effect against dopamine mediated inhibition of mitochondrial respiratory chain activity. However, both H2O2 scavenging and quinone scavenging properties of N-acetylcysteine probably account for its protective effect against Na+,K+-ATPase inhibition induced by dopamine. The results have important implications in the neuroprotective therapy of sporadic Parkinson's disease since inactivation of mitochondrial respiratory activity and Na+,K+-ATPase may trigger intracellular damage pathways leading to the death of nigral dopaminergic neurons.

PMID:18569015[PubMed - indexed for MEDLINE]

Lipoic acid and N-acetyl cysteine decrease mitochondrial-related oxidative stress in Alzheimer disease patient fibroblasts.
Moreira PI, Harris PL, Zhu X, Santos MS, Oliveira CR, Smith MA, Perry G.
SourceCenter for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.

Abstract
In this study, we evaluated the effect of lipoic acid (LA) and N-acetyl cysteine (NAC) on oxidative [4-hydroxy-2-nonenal, N(epsilon)-(carboxymethyl)lysine and heme oxygenase-1] and apoptotic (caspase 9 and Bax) markers in fibroblasts from patients with Alzheimer disease (AD) and age-matched and young controls. AD fibroblasts showed the highest levels of oxidative stress, and the antioxidants, lipoic acid (1 mM) and/or N-acetyl cysteine (100 microM) exerted a protective effect as evidenced by decreases in oxidative stress and apoptotic markers. Furthermore, we observed that the protective effect of LA and NAC was more pronounced when both agents were present simultaneously. AD-type changes could be generated in control fibroblasts using N-methylprotoporphyrin to inhibit cytochrome oxidase assembly indicating that the the oxidative damage observed was associated with mitochondrial dysfunction. The effects of N-methylprotoporphyrine were reversed or attenuated by both lipoic acid and N-acetyl cysteine. These data suggest mitochondria are important in oxidative damage that occurs in AD. As such, antioxidant therapies based on lipoic acid and N-acetyl cysteine supplementation may be promising.

PMID:17917164[PubMed - indexed for MEDLINE]

Disruption of nerve cells may lead to Parkinson's disease
Published: Friday, May 13, 2011, 20:24 IST
Place: Washington, DC | Agency: ANI

Researchers at the Washington University School of Medicine have revealed why Parkinson's disease selectively harms brain cells which produce the chemical dopamine.

Dopamine is involved in brain cell communications including the signals that control movement. As Parkinson's kills the dopamine-producing cells, patients begin to develop tremors, problem in moving and other symptoms.

The new study shows that a drug known to damage dopamine-producing nerve cells and mimic Parkinson's disease does so by rapidly damaging cellular energy generators called mitochondria.

This damage impairs the ability of mitochondria to circulate around the cell as they normally would. As a result, axons, the extended arms nerve cells used to send messages, wither. A few days later, the body or main portion of the cell also dies.

"Much of the research into Parkinson's disease treatments is focused on saving the bodies of these cells, but our results suggest that keeping axons healthy also is essential," says Karen O'Malley of Washington University School of Medicine in St. Louis.

"When axons die back, dopamine is no longer delivered to the neurons that need it. The cell body also has fewer connections to other cells and it needs those connections to survive," she added.

She compared the axon's system for transporting supplies to a railroad. Mitochondria are part of the railroad's cargo. They supply the energy that allows the axon to do its work.

For the study, O’Malley gave cultured mouse nerve cells, a toxin called MPP+ that causes Parkinson's-like symptoms.

She found that the toxin stopped the movement of mitochondria in the axon in 30 minutes. The railroad still functioned, shipping other cargo to the end of the axon. But most mitochondria either stopped moving or were headed for the cell body instead of the axon.

Scientists screened several compounds to see if they could block the toxin's effects. They discovered that only two antioxidants, glutathione and N-acetyl cysteine worked.

N-acetyl cysteine has already been shown to be effective in animal models of Parkinson's disease and is used as a treatment for other disorders in patients.

The study has been published in The Journal of Neuroscience.

Thanks Imark. It is so encouraging to find something that we have a little control over!
I thought it particularly interesting to read that the
protective effects were more pronounced when both N-A-C and LA were present.
I wanted to mention also that I just read in the MAY 2011 issue of Total Wellness that Dr. Sherry Rogers publishes that "...supplements that contain alpha lipoic acid or even worse just lipoic acid are only 50% used by the body, whereas R-lipoic Acid is 100%."
So, I think I'll see if I can find the R-lipoic Acid and take it at the same time as the N-A-C.

Victoria,
I take 100 mg Alpha lipoic acid daily.
But again I have no idea if it is doing any thing!!
cheers
Imad