http://www.google.com/hostednews/afp...tpS5v9uzdf2alw
Some thing new??

WASHINGTON (AFP) — Boosting the output of a protein produced by brain cells called astrocytes can provide complete protection from Parkinson's disease, a study published Monday showed.

A movement disorder characterized by tremors and sluggishness, Parkinson's disease occurs when dopamine-producing nerve cells in a part of the brain called the substantia nigra die or become impaired, making the body's muscles less able to function smoothly and in a coordinated manner.

Boxer Muhammad Ali, actor Michael J. Fox and the late pope John Paul II are among well-known sufferers of the disease.

In the study, the results of which were published in the Proceedings of the National Academy of Sciences, researchers at the University of Wisconsin-Madison studied mice with astrocytes that produced twice the normal level of a protein called Nrf2.

Even when the mice were pumped full of a chemical known to cause Parkinson's disease they were completely protected from the movement disorder, the study showed, concluding that it was the Nrf2 protein produced by the astrocytes which shielded the mice from the chemical's toxic effects.

Pei-Chun Chen, a postdoctoral fellow from Taiwan, crossed the mouse that over-produced Nrf2 with another mouse in which the protein was "knocked out," and found that the "knock-out" mouse was also completely protected from the chemical toxicity which causes Parkinson's disease.

"The dopamine metabolite level was reduced by 90 percent in the knock-out mouse, but it was completely untouched with Nrf2 in astrocytes" and did not develop Parkinson's, said Jeffrey Johnson, a professor in pharmaceutical sciences at the University of Wisconsin who led the study.

"We didn't expect the complete abolition of toxicity," Johnson told AFP.

In December, University of Wisconsin scientists found that increasing Nrf2 could delay the onset of amyotrophic lateral sclerosis, or Lou Gehrig's disease, and studies are ongoing to determine the effect of the protein on sufferers of the neuro-degenerative Alzheimer's and Huntington's diseases.

"My instinct is that astrocyte dysfunction is probably common to all these diseases," Johnson said.

"It's becoming apparent that astrocyte dysfunction is a major contributing factor to the neurons dying," Johnson said.

"If we can make the astrocyte better or stronger, or so that it doesn't become dysfunctional, you can preserve the neurons," he said.

The researchers have begun long-term experiments in mice to see if intervention to reverse Parkinson's is possible after damage has already occurred.

gut disease, Cogane, gene therapy, stem cells, we sure have a lot of bases covered and you cannot argue with the breadth and diversity of research.

On the other hand, as shown in the diagnosis thread, we can't even dx pd in a scientific manner so all the aforementioned could be seen as shooting in the dark.

Depends whether you're a glass half full or empty guy I guess

Neil.

An old drug, deprenyl (Selegiline), affects the production of nrf2 and may offer neuroprotection.

Novel cytoprotective mechanism of anti-parkinsonian drug deprenyl: PI3K and Nrf2-derived induction of antioxidative proteins 2005

Neuroprotection has received considerable attention as a strategy for the treatment of Parkinson’s disease (PD). Deprenyl (Selegiline) is a promising candidate for neuroprotection; however, its cytoprotective mechanism has not been fully clarified. Here, we report a novel cytoprotective mechanism of deprenyl involving PI3K and Nrf2-mediated induction of oxidative stress-related proteins. Deprenyl increased the expression of HO-1, PrxI, TrxI, TrxRxI, γGCS, and p62/A170 in SH-SY5Y cells. Deprenyl also induced the nuclear accumulation of Nrf2 and increased the binding activity of Nrf2 to the enhancer region of human genomic HO-1. The Nrf2-mediated induction of antioxidative molecules was controlled by PI3K. Indeed, furthermore, neurotrophin receptor TrkB was identified as an upstream signal for PI3K–Nrf2 activation by deprenyl. These results suggest that the cytoprotective effect of deprenyl is, in part, dependent on Nrf2-mediated induction of antioxidative proteins, suggesting that activation of the PI3K–Nrf2 system may be a useful therapeutic strategy for PD.

http://www.sciencedirect.com/science...19ef5d0b3f5158

In vivo modulation of the Parkinsonian phenotype by Nrf2

2006

Neal C. Burtona, Thomas W. Kenslera and Tomás R. Guilarte

Oxidative stress has been implicated in the etiology of Parkinson's disease (PD) and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of PD. In this report we show that Nrf2, a transcription factor that regulates the expression of phase 2 and antioxidative enzymes, modulates MPTP neurotoxicity in rodents.

Nrf2 knockout and wild-type mice were administered MPTP doses ranging from 20 to 60 mg/kg.

Seven days after MPTP administration dopamine transporter (DAT) levels were measured using [125I]-RTI-121 quantitative autoradiography as an index of dopamine terminal integrity in the striatum.

The results indicate that MPTP administration resulted in a greater loss of DAT levels in the striatum of Nrf2 knockout mice than in wild-type at all MPTP doses tested.

Activation of the Nrf2 pathway by oral administration of the Nrf2 inducer 3H-1,2-dithiole-3-thione (D3T) to wild-type mice produced partial protection against MPTP-induced neurotoxicity. The protective effect of D3T was not due to a change in MPTP metabolism since the level of the MPTP metabolite MPP+ was not significantly different in the D3T treated striatum relative to vehicle control. Administration of D3T to Nrf2 knockout mice did not protect against MPTP neurotoxicity suggesting that the Nrf2 pathway is necessary for the D3T-mediated attenuation of MPTP neurotoxicity.

This study demonstrates the significance of activating intrinsic antioxidative mechanisms in an in vivo model of neurodegeneration. The in vivo activation of the Nrf2 pathway in the brain may be an important strategy to mitigate the effects of oxidative stress in neurodegenerative disorders and neurological disease.

http://www.sciencedirect.com/science...9c24758ecee34e

My glass is half empty; but it's all champagne.

Jon

My dad took bromocriptine in the 90's, if memory serves.

March 2008:

"The dopamine agonist bromocriptine is used clinically for PD therapy. In addition to ameliorating the motor deficit via dopamine D2 receptor activation, bromocriptine also has neuroprotective and antioxidative activity.......

"Bromocriptine increases the expression and nuclear translocation of a basic leucine zipper transcription factor, nuclear factor-E2-related factor-2 (Nrf2), which is known to be involved in the regulation of numerous antioxidant enzymes via the antioxidant response element.

The Nrf2-related cytoprotective and antioxidative effects of bromocriptine are PI3K/Akt pathway-dependent, and are independent of dopamine receptor activation."

Bromocriptine activates NQO1 via Nrf2-PI3K/Akt signaling: Novel cytoprotective mechanism against oxidative damage

http://www.sciencedirect.com/science...c1087e95861ebc

Best way to be Jon