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- Mitochondrial Dysfunction -


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Mitochondrial Dysfunction

See also,
    Dr. Sinatra
    More posts by Dr. Newport
    Multifunctional Cocktail
          Anti-oxidant trio therapy [?]
    Methylene Blue
    ALA
    Cognisure
    Parkinson's Disease

"It could be that the cells are so depleted of the various substances they need to make energy inside the cell that the cells don't recover simply by providing ketone. I learned more about other disease processes where there is also a problem with energy production in mitochondria, the organelles inside of the cells that manufacture ATP (adenosine triphosphate), the very basic energy that drives the whole function of the cell. Each cell has hundreds to thousands of mitochondria."

The article below talks about research into the role of amyloid-beta proteins in creating nitric oxide, which then damages the "powerhouse" of the cell, the mitochondria. Could this be why neurons then have a problem with glucose metabolism, and why MCTs help?

I remember reading another article about how LOW concentrations of methylene blue may help preserve mitochondrial function: "the drug slows cellular aging and enhances mitochondrial function". The concentration is reported to be ridiculously low (meaning, more research into the original paper is warranted.) But, if it is true that very dilute methylene blue solutions are beneficial, then I have an "act of desperation" option: Kordon's 2.3% Methylene Blue solution... for fish! If a "very low concentration -- about the equivalent of a few raindrops in four Olympic-sized swimming pools of water" would be effective, then what about a drop of fish aquarium methylene blue in a gallon or five of drinking water?

But even if you were to decide on going with laboratory-grade MB, which is a bit pricey, at this level of concentration, a small quantity of MB would last years.

Here are the articles:

Alzheimer's Disease Linked To Mitochondrial Damage
ScienceDaily (Apr. 2, 2009)
Investigators at Burnham Institute for Medical Research (Burnham) have demonstrated that attacks on the mitochondrial protein Drp1 by the free radical nitric oxide—which causes a chemical reaction called S-nitrosylation—mediates neurodegeneration associated with Alzheimer's disease. Prior to this study, the mechanism by which beta-amyloid protein caused synaptic damage to neurons in Alzheimer's disease was unknown... These findings suggest that preventing S-nitrosylation of Drp1 may reduce or even prevent neurodegeneration in Alzheimer's patients. The paper was published in the April 3 issue of the journal Science... The team of scientists, led by neuroscientist and clinical neurologist Stuart A. Lipton, M.D., Ph.D., director of the Del E. Webb Center for Neuroscience, Aging and Stem Cell Research, showed that S-nitrosylated Drp1 (SNO-Drp1) facilitates mitochondrial fragmentation, damaging regions of nerve cell communication called synapses. Mitochondria are the energy storehouses of the cell, and their compromise by excessive fragmentation causes synaptic injury and eventual nerve cell death. Synapses are critical for learning and memory and their impairment leads to the dementia seen in Alzheimer's patients...
http://www.sciencedaily.com/releases/2009/04/090402143453.htm


Interesting research suggests that maybe "free radicals" may not be as big of a problem...

Free Radicals Good for You? Banned Herbicide Makes Worms Live Longer

ScienceDaily (Dec. 20, 2010) — It sounds like science fiction – Dr. Siegfried Hekimi and his student Dr Wen Yang, researchers at McGill’s Department of Biology, tested the current “free radical theory of aging” by creating mutant worms that had increased production of free radicals, predicting they would be short-lived. But they lived even longer than regular worms! Moreover, their enhanced longevity was abolished when they were treated with antioxidants such as vitamin C...
http://www.sciencedaily.com/releases/2010/12/101220084442.htm

Methylene blue...

Potential Alzheimer's, Parkinson's Cure Found In Century-old Drug
ScienceDaily (Aug. 18, 2008)
A new study conducted by researchers at Children's Hospital & Research Center Oakland shows that a century-old drug, methylene blue, may be able to slow or even cure Alzheimer's and Parkinson's disease. Used at a very low concentration – about the equivalent of a few raindrops in four Olympic-sized swimming pools of water – the drug slows cellular aging and enhances mitochondrial function, potentially allowing those with the diseases to live longer, healthier lives.

Methylene blue, first discovered in 1891, is now used to treat methemoglobinemia, a blood disorder. But because high concentrations of methylene blue were known to damage the brain, no one thought to experiment with low concentrations. Also, drugs such as methylene blue do not easily reach the brain...
http://www.sciencedaily.com/releases/2008/08/080818101335.htm

This also begs the question, as I've stated before, that if such an unimaginably small concentration of MB can be beneficial, can comparatively dilute solutions of other chemicals in our water, food, or environment be harmful?

Another point I would like to make is that there are steps to the disease process. All of these things we have discussed appear to interrupt different stages. So even if low-concentration MB is effective, other steps of the disease process, once set in motion, may still progress. I'm thinking of this in relation to why attacking the amyloid beta plaque problem doesn't seem too effective. Perhaps it really is, in the long term, or if the therapy was started early enough before symptoms appeared. But once symptoms appear, there is a whole freight train of other ones in motion. So, snipping off the locomotive without activating the breaks on the box cars means that the train will keep rolling on and on for a long, long time.

Early Role of Mitochondria in Alzheimer's Disease May Help Explain Limitations to Current Beta Amyloid Hypothesis

ScienceDaily (Oct. 13, 2010) — Before Alzheimer's patients experience memory loss, the brain's neurons have already suffered harm for years... A new study in mouse models by researchers at Columbia University Medical Center has found that the brain's mitochondria -- the powerhouses of the cell -- are one of the earliest casualties of the disease. The study, which appeared in the online Early Edition of PNAS, also found that impaired mitochondria then injure the neurons' synapses, which are necessary for normal brain function.

"The damage to synapses is one of the earliest events in Alzheimer's disease, but we haven't been able to work out the events that lead to the damage. Our new findings, along with previous research, suggest that mitochondrial changes harm the synapses, and that we may be able to slow down Alzheimer's at a very early stage by improving mitochondrial function."

Drugs that restore mitochondria function may be able to treat Alzheimer's disease in its earliest stages. One potential drug, cyclosporin, is already used in organ transplant and autoimmune patients. Cyclosporin suppresses the immune system, but it also blocks amyloid beta (Aβ) peptides-induced mitochondrial injury, Dr. Yan has found in previous studies (Du et al. Nature Medicine, 2008).

Cyclosporin, however, has too many toxic side effects for long term use in other patients...

Most Alzheimer's researchers initially believed that Aβ peptides caused the disease after aggregating together in large, extracellular plaques, a defining feature of Alzheimer's-affected brains. But Dr.Yan's findings, along with those of many other scientists, now point to an earlier role for Aβ peptides inside the brain's neurons.

The mitochondria are damaged, the researchers found, when (Aβ) peptides breach the mitochondria's walls and accumulate on the inside. Even low concentrations of Aβ peptides, equivalent to the levels found in cells years before symptoms appear, impair the mitochondria, particularly mitochondria that supply power to the neuron's synapses.

When filled with Aβ peptides, these synaptic mitochondria were unable to travel down the neurons' long axons to reach, and fuel, the synapse. And the mitochondria that did make the journey failed to provide adequate energy to operate the synapses. Without operating synapses, neurons are unable to function.

"Since cyclosporin is already FDA approved for use in organ transplant and autoimmune patients, this research has the potential to lead to more rapid clinical trials and progress quickly," said Dr. Yan...
http://www.sciencedaily.com/releases/2010/10/101013122557.htm
   

In Parkinson's Disease, Brain Cells Abandon Mitochondria
ScienceDaily (Oct. 8, 2010) — In a study that sheds new light on the causes of Parkinson's disease, researchers report that brain cells in Parkinson's patients abandon their energy-producing machinery, the mitochondria. A shutdown in fuel can have devastating effects on brain cells, which consume roughly 20 percent of the body's energy despite making up only 2 percent of body weight... researchers, now show that a root cause of Parkinson's disease may lie in 10 gene sets related to energy production that spur neurons in the brain to "divorce" their mitochondria and related energy-producing pathways..."The most exciting result from our study for me is the discovery of PGC-1alpha as a new therapeutic target for early intervention in Parkinson's disease. PGC-1alpha is a master switch that activates hundreds of mitochondrial genes, including many of those needed to maintain and repair the power plants in the mitochondria,"... FDA-approved medications [Actos, CoQ10] that activate that PGC-1alpha are already available for widespread diseases like diabetes. These medications may jumpstart the development of new Parkinson's drugs; instead of having to start from scratch, pharmaceutical companies may be able to dust off their drug libraries and find look-alike drugs capable of targeting PGC-1alpha in the brain. "As we wrap up our first year of publishing the journal, the new study from Zheng et al. exemplifies the goal of Science Translational Medicine, applying knowledge and technology from different fields-such as neuroscience, genomics and bioinformatics-to achieve new discoveries,"...
http://www.sciencedaily.com/releases/2010/10/101006151557.htm
[See also Medium Chain Triglycerides (MCT oils) and Glucose Metabolism]

Brain Might Be Key to Leptin's Actions Against Type 1 Diabetes, Researchers Find
ScienceDaily (Nov. 14, 2010)

New findings by UT Southwestern Medical Center researchers suggest a novel role for the brain in mediating beneficial actions of the hormone leptin in type 1 diabetes... They found that infusing leptin into the lateral ventricle of the animals' brains reversed the lethal consequences of type 1 diabetes. The results establish the brain as a potentially critical site for mediating the metabolism-improving actions of leptin,...
http://www.sciencedaily.com/releases/2010/10/101019171711.htm


As mentioned earlier, one inherits their mitochondria from their mothers...

Alzheimer's Disease Inherited Through Maternal Line, Study Finds
ScienceDaily (Nov. 15, 2010)

"Our data indicate that adult children of mothers with Alzheimer's may be at increased risk for developing the disease.  It is therefore extremely important to understand the genetic mechanisms involved in maternal transmission of Alzheimer's disease, which are currently unknown. Identifying a genetic predictor for the disease might lead to preventive treatments years before the onset of clinical symptoms."
http://www.sciencedaily.com/releases/2010/11/101115111007.htm


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Updated: July 2, 2012
Inception: July 2, 2012