New Studies and Articles Added:

Oxidative Stress and Diabetic Complications
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Defective Nrf2-dependent redox signalling contributes tomicrovascular dysfunction in type 2 diabetes
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Bioactive food components prevent carcinogenic stress via Nrf2 activation in BRCA1 deficient breast epithelial cells
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New studies and articles posted:

Genomic Structure and Variation of Nuclear Factor (Erythroid-Derived 2)-Like 2
(Link to entire article)

Vascular oxidative stress in aging: a homeostatic failure due to dysregulation of NRF2-mediated antioxidant response
(Link to entire article)

Prevention of Diabetic Complications by Activation of Nrf2:
Diabetic Cardiomyopathy and Nephropathy
(Link to entire article)

Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) is a novel
therapeutic target for diabetic complications
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The role of the antioxidant and longevity-promoting Nrf2
pathway in metabolic regulation

(Link to entire article)

New Page Added

We have added a new tab with information containing different studies regarding oxidative stress and Nrf2 and how they relate to different diseases. This is for informational purposes only and were not saying Protandim "diagnoses, treats, cures or prevents any diseases." You must draw your own conclusions.
Jump to "Nrf2/Oxidative Stress Sudies" Tab

Nrf2 Activation, an Innovative Therapeutic Alternative in Cerebral Ischemia

From  "Advances in the Preclinical Study of Ischemic Stroke", book edited by Maurizio Balestrino, ISBN 978-953-51-0290-8, Published: March 16, 2012 under CC BY 3.0 license

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Nrf2, a Guardian of Healthspan and Gatekeeper of Species Longevity

An interesting study of the Nrf2 pathway and its role in protection from oxidative stress and inflamation; its role in health and longevity
From Oxford Journals' Integrative and Comparative Biology
Integr Comp Biol. 2010 November; 50(5): 829–843.

Published online 2010 May 6. doi:

Abstract
Although aging is a ubiquitous process that prevails in all organisms, the mechanisms governing both the rate of decline in functionality and the age of onset remain elusive. A profound constitutively upregulated cytoprotective response is commonly observed in naturally long-lived species and experimental models of extensions to lifespan (e.g., genetically-altered and/or experimentally manipulated organisms), as indicated by enhanced resistance to stress and upregulated downstream components of the cytoprotective nuclear factor erythroid 2-related factor 2 (Nrf2)-signaling pathway. The transcription factor Nrf2 is constitutively expressed in all tissues, although levels may vary among organs, with the key detoxification organs (kidney and liver) exhibiting highest levels. Nrf2 may be further induced by cellular stressors including endogenous reactive-oxygen species or exogenous electrophiles. The Nrf2-signaling pathway mediates multiple avenues of cytoprotection by activating the transcription of more than 200 genes that are crucial in the metabolism of drugs and toxins, protection against oxidative stress and inflammation, as well as playing an integral role in stability of proteins and in the removal of damaged proteins via proteasomal degradation or autophagy. Nrf2 interacts with other important cell regulators such as tumor suppressor protein 53 (p53) and nuclear factor-kappa beta (NF-κB) and through their combined interactions is the guardian of healthspan, protecting against many age-related diseases including cancer and neurodegeneration. We hypothesize that this signaling pathway plays a critical role in the determination of species longevity and that this pathway may indeed be the master regulator of the aging process.

Link to entire article via PubMed

Protandim “most suited as a therapeutic strategy” when compared to BG-12, a.k.a Tecfidera, according to a Biogen funded study.

Nrf2 activators: a novel strategy to promote oligodendrocyte survival in multiple sclerosis? J. Lim, S. van der Pol, J. Drexhage, E. de Vries, J. van Horssen (Amsterdam, NL) Objectives: To investigate the potential of different Nrf2 activators to boost antioxidant enzyme expression in oligodendrocytes and protect them from reactive oxygen species (ROS)-mediated cell death. Background: Oligodendrocyte damage and loss are key features of Multiple Sclerosis (MS) pathology and oligodendrocytes are particularly vulnerable to ROS-induced oxidative damage and cell death. Hence, a potential therapeutic strategy to protect these cells from ROS-mediated damage is urgently needed. To date, several compounds, including fumurate derivative BG-12, tert-Butylhydroquinone (tBHQ), sulforaphane (SFN) and protandim have potential anti-inflammatory and neuroprotective properties. These compounds are thought to exert their protective function via activation of the nuclear-factor-E2-related factor-2 (Nrf2) transcriptional pathway, which is involved in the production of antioxidant enzymes necessary for oxidative stress defense. We postulate that distinct Nrf2 activators boost antioxidant enzyme production in oligodendrocytes and limit ROS-mediated oligodendrocyte cell death. Methods: Primary rat oligodendrocytes and rat and human oligodendrocyte cell lines were treated with different concentrations of BG-12, tBHQ, SFN and protandim. Next, we analyzed the expression of Nrf2-mediated antioxidant enzymes by PCR and Western blot techniques. To study the beneficial effects of the different Nrf2 activators, we first incubated the oligodendrocytes with Nrf2 activators and subsequently exposed them to various concentrations of hydrogen peroxide and measured oligodendrocyte cell survival. Results: 1. BG-12, tBHQ, SFN and protandim are well-tolerated and strongly induce Nrf2-driven antioxidant enzyme production in oligodendrocytes, with protandim showing the most potent induction.  2. Nrf2 activators are able to protect oligodendrocytes against ROS-induced cytotoxicity. Conclusions: Our findings indicate that several Nrf2 activators are able to significantly increase antioxidant enzyme production in oligodendrocytes. Interestingly, protandim, a dietary supplement consisting of herbal ingredients, was the most potent inducer and therefore may be the most suited as a therapeutic strategy. Importantly, Nrf2-mediated antioxidant enzyme expression in oligodendrocytes resulted in enhanced oligodendrocyte survival during an oxidative attack. Dr. J. van Horssen received research grants from BiogenIdec

Link to abstract from 5th Joint triennial congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis Amsterdam, The Netherlands 19.10.2011 - 22.10.2011

3rd Oral Drug to Treat MS Is Approved by the F.D.A.

By ANDREW POLLACK

Published: March 27, 2013

A chemical once used to treat sofas — until it was found to causerashes and blisters in people who sat on them — is now poised to become a major therapy for multiple sclerosis.

The new pill for multiple sclerosis is made by Biogen Idec.

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The Food and Drug Administration on Wednesday approved the chemical, dimethyl fumarate, which will be sold by Biogen Idec under the name Tecfidera, the third of a spate of oral drugs that are transforming the treatment of multiple sclerosis.

Despite the drug’s seemingly odd history, Wall Street analysts, doctors and patients expect Tecfidera to become a blockbuster because of its combination of efficacy and relative safety and the convenience of being a pill. Doctors and analysts say some patients have been putting off starting treatment until Tecfidera is available.

Feedback from doctors was “highly positive, with a strong consensus that Tecfidera offers a more favorable clinical profile than other oral or injectable first-line options,” Thomas Wei, an analyst at Jefferies, wrote on Monday.

About 400,000 Americans and more than two million people worldwide have multiple sclerosis, many of them women first stricken in their 20s. The disease is believed to occur when the body’s immune system attacks the insulation around nerve fibers, causing symptoms like difficulty walking, blurred vision and fatigue.

The market for MS drugs is already $14 billion annually, with $8.5 billion of that in the United States, according to Sanford C. Bernstein & Company.

While self-injected medicines like Avonex from Biogen and Copaxone from Teva that entered the market in the 1990s are still used by the majority of treated patients, newer oral drugs are making inroads. In addition to Tecfidera, the other two oral drugs are Gilenya from Novartis, approved in 2010, and Aubagio from Sanofi, approved in September.

The approvals will solidify Biogen’s position as a leader in multiple sclerosis drugs. In addition to Tecfidera and Avonex, the company also sells Tysabri, a highly effective intravenous drug but one that can cause a potentially fatal brain infection.

Biogen shares have more than doubled in the last two years, largely because of anticipation about Tecfidera. The shares closed on Wednesday at $182.68, up about 3 percent.

Biogen, which is based in Weston, Mass., did not immediately announce the price of Tecfidera, which was known as BG-12 during its development.

Stock fund portfolio managers polled by the research firm the ISI Group on Wednesday predicted a price of about $51,000 a year, which would be roughly in line with prices of the injectable drugs, but less than the $60,000 a year list price of Gilenya.

The effectiveness of multiple sclerosis drugs is often judged by how much they reduce the frequency of relapses, which are severe flare-ups of symptoms, compared to a placebo in clinical trials.

The injectable drugs reduced the frequency about 30 percent, as did the new oral drug Aubagio. Gilenya cut the rate about 54 percent.

Tecfidera cut the relapse rate 44 percent in one trial and 53 percent in another, which might put it a bit behind Gilenya. Tecfidera is also taken twice a day, while Gilenya is taken only once daily.

But Gilenya has side effects that make it off limits for some patients and require careful testing and monitoring for heart, liver and eye problems. Patients are supposed to remain in a medical facility for at least six hours after taking their first dose to make sure their heart does not slow down too much.

Tecfidera will have fewer restrictions and testing requirements. The prescribing information does recommend that blood cell levels be tested before a patient starts on the drug and annually thereafter. That is because Tecfidera can reduce white blood cell levels, leaving patients potentially vulnerable to infections. And some studies in animals suggest that the drug might cause fetal harm, making it a questionable choice for pregnant women, the label says.

Tecfidera’s most common side effect is flushing, which occurs in about 40 percent of patients. The drug can also cause nausea and diarrhea.

Dimethyl fumarate and some closely related compounds are simple molecules that have been used as food additives. The compound was also used to protect upholstery and shoes from mold during storage. But people in Europe developed skin irritation and other problems, causing its use in consumer goods to be banned there.

The first use of it in medicine was in 1959, when a German chemist treated his ownpsoriasis. A drug called Fumaderm, which is similar to Tecfidera, was approved to treat psoriasis in Germany in 1994.

It is not quite clear how Tecfidera works. It is thought that one way is to activate a pathway known as Nrf2, which helps protect the body from oxidative stress.

Geoffrey C. Porges, a biotechnology analyst at Sanford Bernstein, said in a note on Monday that he expected global sales to reach $1.7 billion by 2015 and $2.6 billion by 2017. European regulators recommended last week that Tecfidera be approved as well.

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