Scientists Find Peptide Therapy Can Prevent Progression Of Parkinson's Disease

15 Nov 2007
http://www.medicalnewstoday.com/articles/88811.php

Researchers have successfully used a peptide to reverse biochemical, cellular and anatomical changes that occur in the brains of mice with Parkinson's disease (PD), and report success in preventing the disease from progression.

"This could be a new approach to halt disease progression in PD patients," said study author Kali Pahan, PhD, professor of neurological sciences at Rush University Medical Center. Dr. Pahan and colleagues from Rush, along with researchers at the University of Nebraska Medical Center, Omaha, and Yale University, New Haven, published these findings in the Proceedings of the National Academy of Sciences of the United States, November 13, 2007.

The authors have shown that one protein, NF-kB, is increased in the midbrain of PD patients and mice with PD pathology, and the researchers used a novel peptide (small proteins) to block this protein in mice with PD-like symptoms.

Pahan explained that after intraperitoneal injection (injection into the abdomen of the mouse) this peptide enters into the brain and blocks protein NF-kB and other associated toxic molecules, and goes on to protects neurons, normalizes neurotransmitter levels, and improves motor functions in mice with PD. Peptides, proteins and certain drugs usually do not enter into the brain after crossing the blood-brain barrier. Therefore, at present, peptides, proteins or genes are injected into the brain which is risky and painful. "To overcome this problem, we have added a tag in front of that peptide that is helping the peptide enter into the brain. Therefore, there is no need to inject these peptides into the brain. This is an important discovery.

Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of PD," Pahan said. "Now we need to translate this finding to the clinic and test this peptide in patients with PD. If these results can be replicated in PD patients, it would be a remarkable advance in the treatment of this devastating neurodegenerative disease."

Parkinson's is a slowly progressive disease that affects a small area of cells within the mid-brain known as the substantia nigra. Gradual degeneration of these cells causes a reduction in a vital chemical neurotransmitter, dopamine. The decrease in dopamine results in one or more of the classic signs of Parkinson's disease that includes: resting tremor on one side of the body; generalized slowness of movement; stiffness of limbs; and gait or balance problems. The cause of the disease is unknown. Both environmental and genetic causes of the disease have been postulated.

Parkinson's disease affects about 1.2 million patients in the United States and Canada. Although 15 percent of patients are diagnosed before age 50, it is generally considered a disease that targets older adults, affecting one of every 100 persons over the age of 60. This disease appears to be slightly more common in men than women.

This research was supported by grants from Michael J. Fox Foundation for Parkinson's Research and National Institutes of Health.

1: J Biol Chem. 1995 Oct 20;270(42):24995-5000.

Erratum in:
J Biol Chem 1995 Dec 15;270(50):30235.

Activation of transcription factor NF-kappa B is suppressed by curcumin
(diferuloylmethane) [corrected]

Singh S, Aggarwal BB.

Department of Molecular Oncology, University of Texas M.D. Anderson Cancer
Center, Houston 77030, USA.

When activated, NF-kappa B, a ubiquitous transcription factor, binds DNA as a
heterodimeric complex composed of members of the Rel/NF-kappa B family of
polypeptides. Because of its intimate involvement in host defense against
disease, this transcription factor is an important target for therapeutic
intervention. In the present report we demonstrate that curcumin
(diferuloylmethane), a known anti-inflammatory and anticarcinogenic agent, is a
potent inhibitor of NF-kappa B activation. Treatment of human myeloid ML-1a cells
with tumor necrosis factor (TNF) rapidly activated NF-kappa B, which consists of
p50 and p65 subunits, and this activation was inhibited by curcumin. AP-1 binding
factors were also found to be down-modulated by curcumin, whereas the Sp1 binding
factor was unaffected. Besides TNF, curcumin also blocked phorbol ester- and
hydrogen peroxide-mediated activation of NF-kappa B. The TNF-dependent
phosphorylation and degradation of I kappa B alpha was not observed in
curcumin-treated cells; the translocation of p65 subunit to the nucleus was
inhibited at the same time. The mechanism of action of curcumin was found to be
different from that of protein tyrosine phosphatase inhibitors. Our results
indicate that curcumin inhibits NF-kappa B activation pathway at a step before I
kappa B alpha phosphorylation but after the convergence of various stimuli.

PMID: 7559628 [PubMed - indexed for MEDLINE]

Now, usually I dismiss reports of experimentation on propriatory blends as suspect at best. But these guys are at one of the best cancer centers in the world. A little searching turned up the ingredients (at the bottom of the page) but the product seems to be readily available as well.


1: Nutr Cancer. 2007;57(1):78-87.

Zyflamend, a polyherbal preparation, inhibits invasion, suppresses
osteoclastogenesis, and potentiates apoptosis through down-regulation of NF-kappa
B activation and NF-kappa B-regulated gene products.

Sandur SK, Ahn KS, Ichikawa H, Sethi G, Shishodia S, Newman RA, Aggarwal BB.

Cytokine Research Laboratory, Department of Experimental Therapeutics, The
University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

Zyflamend, a polyherbal preparation, was designed based on constituents that
exhibit antiproliferative, antiinflammatory, antioxidant, antiangiogenic, and
apoptotic activities through a mechanism that is not well defined. Because the
nuclear factor (NF)-kappaB has been shown to regulate proliferation, invasion,
and metastasis of tumor cells, we postulated that Zyflamend modulates the
activity of NF-kappa B. To test this hypothesis, we examined the effect of this
preparation on NF-kappaB and NF-kappaB-regulated gene products. We found that
Zyflamend inhibited receptor activator of NF-kappa B ligand-induced
osteoclastogenesis, suppressed tumor necrosis factor (TNF)-induced invasion, and
potentiated the cytotoxicity induced by TNF and chemotherapeutic agents, all of
which are known to require NF-kappa B activation. Zyflamend suppressed NF-kappa B
activation induced by both TNF and cigarette smoke condensate. The expression of
NF-kappa B-regulated gene products involved in antiapoptosis
(inhibitor-of-apoptosis protein 1/2, Bcl-2, Bcl-xL, FADD-like
interleukin-1betaconverting enzyme/caspase-8 inhibitory protein, TNF
receptor-associated factor-1, and survivin) and angiogenesis (vascular
endothelial growth factor, cyclooxygenase-2, intercellular adhesion molecule, and
matrix metalloproteinase-9) was also down-regulated by Zyflamend. This correlated
with potentiation of cell death induced by TNF and chemotherapeutic agents.
Overall, our results indicate that Zyflamend suppresses osteoclastogenesis,
inhibits invasion, and potentiates cytotoxicity through down-regulation of
NF-kappa B activation and NF-kappa B-regulated gene products.

PMID: 17516865 [PubMed - indexed for MEDLINE]


Zyflamend 120 has the following phytonutrients:
Basil (Ocimum sanctum) contains ursolic acid, which may enhances detoxification and support the inflammation response.

Turmeric is a unique curcumin phytonutrient complex that may have additional benefit when combined with green tea polyphenols.

Ginger extract offers numerous beneficial constituents.

Green tea has potent polyphenols and has been praised highly by scientists and the media.

Rosemary herb is starting to become more popular.

Hu Zhang: (Polygonum cuspidatum) is an herb that has one of the richest known content of resveratrol, a compound that has been found in rodents to have potential anti-aging properties.

Chinese Goldthread and Barberry has a unique berberine phytonutrient complex, naturally supports the inflammation response system.*

Oregano is a source of large number of compounds that promote a healthy inflammatory response.

Scutellaria: scullcap: Unique baicalin phytonutrient complex, naturally supports healthy inflammatory responses.

I tried to summarize the excellent postings of this thread as follows:
1)Recent research (15 Nov 2007) discovers a novel peptide which blocks a toxic protein, NF-kB and in this way protects neurons, normalizes neurotransmitter levels, and improves motor functions in mice with PD.
2)1995 research results indicate that curcumin inhibits NF-kappa B activation
3)Nutr Cancer. 2007;57(1):78-87 :Zyflamend, a polyherbal preparation, inhibits invasion, suppresses osteoclastogenesis, and potentiates apoptosis through down-regulation of NF-kappa B activation and NF-kappa B-regulated gene products.
When I last visited my PD specialist few months back he “assured” there is nothing which can slow down PD ! I am sure he is too busy to follow up research such as above.
By the way, and based on other Google search, I have been adding a spoonful of tumeric to my dish even though my wife complains that I am spoiling the delicate taste of her cooking !

Turmeric has some pretty powerful effects on some folks if taken too much. My wife, for example, became suicidally depressed after a week or so of heavy use. I would stick to a reasonable dose, whatever that might be, particularly if I was "high strung".

As for myself, I'm going to try to order some of the mixed extracts from earlier in the thread. I'm already familiar with more than half and the mix has had some testing. There is a lot of room for synergy there too.

It all comes back to the hypothesis that exposure in the womb to bacterial toxins sets up a immune response in the nervous system. That triggers the production of the NF-kB and a host of others. A lot more detail can be found here.

As for the neuros, I suggested to mine that stress was a factor and she dismissed it out of hand. I colulda strangled her but the stress made mefreeze.