I am working on a project searching for drugs from plants against Alzheimer disease. Do you think we can have a success?

Paul Moundipa on Nov 17, 2015 • 4 answer
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Thank you for the question, Paul.
I think this is an interesting idea but it is hard to say for sure how successful an approach like this will be without more information. For example, what type of compounds are you looking for? How do you plan to screen these compounds once you’ve isolated them and what endpoints do you plan to assess? Do you have any indication that certain plants may have effects on any AD-related pathology (e.g. Aβ accumulation, neurofibrillary tangle deposition, γ-secretase activity, etc.) or is this purely an exploratory study?
Thanks again for the question.

Tim Spencer on Nov 17, 2015
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I would expand on Tim Spencer's answer. I think the success of a search for natural products that will be effective against Alzheimer's will depend entirely on your screen -- the 'endpoints'. Looking for amyloid-related changes (less Abeta and phosphotau) would be worthwhile, but equally important would be the model system in which you choose to look at these endpoints. I can't be of much help here. As I've written, I'm not confident of the validity of any of our current AD mouse models and increasingly, I'm worried that our in vitro models have problems of their own. I would urge you to be patient with whatever model you choose. Alzheimer's takes time to emerge from healthy brain aging and takes even more time to reveal its full cellular phenotype. Try and build 'age' into whatever system you look at.

But good luck.

Dr. Karl Herrup on Nov 18, 2015
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That's an interesting but deceptively and one might say even fantastically complex question. Part of the problem is that almost every conceivable type of organic molecule can be found in plants. So, as others have pointed out, out of that enormous complexity you've got to narrow your focus quite a bit. That being said, I have to believe that polyphenols, while as a single therapy have not been terribly successful, may have an underappreciated role in prevention. Speaking of single therapy approaches, I believe the field has been totally captured by what is now looking more and more like a manifestly false idea: that there is going to be a single compound that "cures" or stops Alzheimer's disease, independently of stage. I don't think that's going to be true, and for that matter, I think we been captured by the assumption that there is such a compound that will stop clinical stages. I'm not sure why we believe that except that we seem to gravitate in relationship to this disease anyway toward single factor or primary factor thinking, when there is nothing in biology that is not intimately recursive. In other words, the amyloid hypothesis in its original form has failed, and need to consider that declining proteostasis and increasing junk protein is interactive with a bunch of other cellular phenotypes of aging including inflammation, mitochondrial decline, deterioration in genomic integrity and increasing genetic damage, and oxidative stress. The notion that one of these cellular phenotypes of aging – increasing junk protein and declining autophagy – is going to explain a disease of aging seems increasingly unlikely. If the amyloid hypothesis is at best a very partial truth, it means that the field can finally open itself to a more multifactorial approach to both prevention and treatment. In that context, all kinds of plant compounds – with their deceptively complex effects on cell signaling and on all the above phenotypes of aging – might all of a sudden be terribly relevant. Part of my interest in polyphenols is that rather than their functioning as some kind of antioxidant sponge (how they are advertised in the media), their real biology is way more complicated, and they have a very diverse footprint of affects on cell signals. Indeed it's impossible to find an area of cell signaling where polyphenols have no impact. What's also relevant in this is that we have gone from an evolutionary pathway in which we consumed enormous amounts of fruits and vegetables – the only real source for polyphenols in our evolutionary diet – to one in which we are eating a higher percentage of processed foods that do not have these compounds. This cannot be a good thing from the standpoint of aging, or any of its diseases. A critical study – yet to be completed – would be to look at the incidence of Alzheimer's disease in the few remaining true hunter gatherer groups that still exist. The work of Eaton and Eaton suggests that at least anecdotally the incidence of cognitive decline in tribal elders is very low compared to Western societies, even when you allow for the increased early mortality in hunter gatherers.

So – short form of a long story – with proper screening of compounds and with a variety of animal and preclinical models, and where we look at targets beyond amyloid and amyloid processing, I believe things are wide-open in terms of the potential relevance of plant compounds for both the prevention and clinical treatment of this deceptively complex disease.

Douglas F Watt on Dec 23, 2015
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Yes sure. You have to look for traditional knowledge where people without knowing scientific background uses herbs for memory enhancement.

Dr Ram Singh on Jan 05, 2016
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