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Reversal of Tau Related Pathology

tau alzhiemers memory

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#1 Infinite1

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Posted 27 June 2018 - 04:12 AM


Here is a rather profound finding published in the Journal of Molecular Neurobiology. Using a common asthmatic drug (Zileuton) there was an observed reversal  in behavioral induces in a small animal model (mouse) of Alzhiemers. Sorry, I'm not able to comment much on this, as I myself am not in possession of full text. If anyone happens to have access please do post for the rest! :)

 

Here is the abstract. Obviously more details about the route of administration would certainly be nice, as otherwise this would be something many might wish to research themselves for the obvious benefits of being easily sourced..not to mention history of prior clinical application with desirable safety profile. https://www.ncbi.nlm...pubmed/29881943

 

Learning Impairments, Memory Deficits, and Neuropathology in Aged Tau Transgenic Mice Are Dependent on Leukotrienes Biosynthesis: Role of the cdk5 Kinase Pathway.

 

Abstract
Previous studies showed that the leukotrienes pathway is increased in human tauopathy and that its manipulation may modulate the onset and development of the pathological phenotype of tau transgenic mice. However, whether interfering with leukotrienes biosynthesis is beneficial after the behavioral deficits and the neuropathology have fully developed in these mice is not known. To test this hypothesis, aged tau transgenic mice were randomized to receive zileuton, a specific leukotriene biosynthesis inhibitor, or vehicle starting at 12 months of age for 16 weeks and then assessed in their functional and pathological phenotype. Compared with baseline, we observed that untreated tau mice had a worsening of their memory and spatial learning. By contrast, tau mice treated with zileuton had a reversal of these deficits and behaved in an undistinguishable manner from wild-type mice. Leukotriene-inhibited tau mice had an amelioration of synaptic integrity, lower levels of neuroinflammation, and a significant reduction in tau phosphorylation and pathology, which was secondary to an involvement of the cdk5 kinase pathway. Taken together, our findings represent the first demonstration that the leukotriene biosynthesis is functionally involved at the later stages of the tau pathological phenotype and represents an ideal target with viable therapeutic potential for treating human tauopathies.



#2 Mind

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Posted 27 June 2018 - 06:16 PM

I would usually say...."in mice" :sad: , because mouse studies a rarely useful for human aging interventions, however the word "reversal" does peak my interest. Now the question is, would it reverse tau pathology in wild mice, to whatever extent they mice up with a similar mental condition in old age.



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#3 resveratrol_guy

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Posted 29 June 2018 - 08:03 AM

Zileuton seems to be sold as Zyflo CR, which is around $33 per 600 mg pill on pharmacychecker.com. I'm not sure what the dose would be in order to achieve the same tau clearance in humans, assuming that it's even possible, but it sounds like thousands of dollars. And good luck obtaining it without a prescription, anywhere in the world. But if you could in fact get past those hurdles, it might do wonders for certain patients.

 

Otherwise, a cheaper and obtainable analog is probably ibudilast, which acts on the same pathway. Lostfalco provides all the details here. There are some user experience reports on Longecity but none of them impressed me much, no doubt because AD is a multifactorial disease which requires many parallel therapies.

 

There's also the tau vaccine trials currently underway. Any clinical use would be years off and devastatingly expensive.

 

Another tau strategy is presented in Turnbuckle's Alzheimers protocol.

 

 



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#4 aribadabar

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Posted 22 July 2018 - 01:40 AM

Full text: http://sci-hub.tw/10...2035-018-1124-7

 







Also tagged with one or more of these keywords: tau, alzhiemers, memory

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