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Neuroscientist is interviewed about Alzheimer's/leukotriene connection on Australian radio (audio)
Larrytherunner
Posted: Saturday, November 25, 2017 10:21 AM
Joined: 2/26/2016
Posts: 229


This audio is really worth listening to. Professor Rubinstein is a really smart guy who has done the research and knows what he is talking about, and Dr Norman Swan MD knows how to ask the right questions. I believe the audio will be well worth your time.

Professor Rubinstein discusses how leukotrienes are involved in Alzheimer's and dementia, as well as in cancer, heart disease and in aging. He also discusses how leukotrienes create reactive oxygen molecules, but eating antioxidant foods and supplements are not effective in counteracting them.

He explains that off patent drugs are available now that are effective in blocking leukotrienes, but it is difficult to find any company or government willing to pay for clinical trials. Fortunately, since the interview, a clinical trial for montelukast (Singulair) has been scheduled for next year, sponsored by the Canadian company Intelgenx, and under the supervision of the Canadian government.

http://www.abc.net.au/radionational/programs/healthreport/leukotrienes-used-block-stress-asthma-free-radicals/7350034


Serenoa
Posted: Sunday, November 26, 2017 6:59 AM
Joined: 4/24/2012
Posts: 484


Thanks. Good interview. There's an excerpt:

Norman Swan: The team at the Weizmann Institute have found a mechanism inside cells which in response to stress like chemo, other chemicals or lack of oxygen, produces these free radicals, the highly damaging forms of oxygen which in effect rust tissues. The key substance in this pathway is called a leukotriene, which you've probably never heard of before unless you have asthma, because leukotrienes are involved in the immune reaction in the lungs which make you wheeze. In other cells, it turns out that leukotrienes are critical to the production of oxidative stress. And as would luck would have it, there are long-standing well proven asthma medications which work by blocking leukotrienes.


Lane Simonian
Posted: Monday, November 27, 2017 9:53 PM
Joined: 12/12/2011
Posts: 4863


I read the transcript and agree with the point that Montelukast acts as an antioxidant--it does so by inhibiting a receptor that leads to inflammation and oxidation.

Other antioxidants scavenge oxidants and reverse part of their damage.  The combination of some of these more potent antioxidants in combination with Montelukast or other drugs which inhibit oxidation and inflammation.

The following is for reducing lung injury but it also applies to Alzheimer's disease.

Protective Effects of Montelukast and L-Carnitine on Cyclophosphamide-Induced Lung Injury

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) productions mediate such injury through peroxidation of membrane lipids, proteins and DNA. CP conjugates with GSH, thus causes oxidative stress through GSH [glutathione] depletion. GSH depletion leads to lowered cellular defense against free radical induced cellular injury resulting in necrotic cell death. The detrimental effects of may also be mediated by stimulating nitric oxide (NO) production. RNS, particular peroxynitrite (ONOO-) produced  through reacting NO and superoxide (O2-), participate massively in oxidative and inflammatory tissue injury. In agreement with the aforementioned explanations, results of the present investigation showed oxidative and nitrosative derangements in CP control group, represented as suppressed GSH levels and antioxidant enzyme activities (GST and SOD) coupled with elevated TBARS and NO2- levels when compared with normal control animals. 

Results of the present investigation clearly show antioxidant potentials for ML and LC, alone or in combination, regarding their effect on GSH, TBARS, GST, SOD and NO2- levels. It seems that LC is a more potent antioxidant agent compared to ML, which is apparent from the significant difference between LC and ML regarding all measured oxidative parameters in the direction of LC being better. In agreement, it was reported that LC might be a good antioxidant through different mechanisms. First, LC can act as a direct free radical scavenger. Second, it is an essential factor for synthesis of adenosine triphosphate (ATP) through mitochondrial fatty acid mobilization and oxidation. At this step of ATP synthesis, a large amount of oxygen is consumed, and the oxygen is reduced to water at the end of the TCA cycle. Then, oxygen concentration decreases and ROS formation is also reduced. Third, LC also might interfere with the ROS formation through chelation of ferrous ion which is a catalyst in free radical generation reactions like Fenton and Haber-Weiss reactions. Finally, LC antioxidant power may be due to its ability to increase activities of antioxidant enzymes like SOD and others. Regarding ML, it was reported to correct  lipopolysaccharide (LPS)-induced elevations in TBARS and depletion in GSH in a lung model of injury.

Find the right combination of antioxidants and Alzheimer's become a chronic rather than a fatal disease.


Larrytherunner
Posted: Wednesday, November 29, 2017 4:39 AM
Joined: 2/26/2016
Posts: 229


Lane, the brain has special protection called the blood brain barrier. Many antioxidants that pass into cells in other parts of the body can not pass through the blood brain barrier. Also you are writing about research coming from many different sources but you are not giving us those sources.
Lane Simonian
Posted: Wednesday, November 29, 2017 10:08 AM
Joined: 12/12/2011
Posts: 4863


There are indeed many problems with polyphenolic antioxidants.  Most but not all make it past the blood-brain barrier because of their small size.   

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372091/

Some polyphenols do no enter the bloodstrem well, some don't enter the fatty tissue of the brain well, some act as pro-oxidants in certain conditions, and some are rapidly metabolized and/or excreted.  But some polyphenols such as found in panax ginseng, essential oils via aromatherapy, and CBD oil likely provide effective treatments for Alzheimer's disease and early on their effectiveness may increase using antioxidant and antiinflammatory drugs such as Montelukast.