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Natural Science Forum / Biology / Biology / July 2008#54 new news on Alzheimers as there are two beta amyloid molecules ; new book: Metal Causation coupled with Weak-Protein-Point ^Theory of Medicine (Alzheimers, Autism, Parkinsons, Prion, Schizophrenia)
The TV news shone a spotlight on Alzheimers yesterday by saying there are two different molecules of beta amyloid in the disease. One molecule is very small and short compared to the other beta amyloid. And those afflicted by the disease seem to be flooded with the small short variety. I tried looking up this new research but was unable to find it. I have a question about this finding. Can mercury metal make beta amyloid shrink in size? Can fluoride or mercury-fluoride make beta amyloid shrink? Now this idea that the disease is of a different type of the molecule from a normal person is intriguing to apply to the other metal diseases such as Prion. In Prion disease the prion protein is well known to have many different types and whether the most damaging prion disease is the smallest prion molecule is a question. Now in Parkinson's disease, the protein involved there does not seem to come in two types where the smallest is the most damaging. Here I have to ask whether mercury compounds can cause protein shrinkage? Archimedes Plutonium www.iw.net/~a_plutonium whole entire Universe is just one big atom where dots of the electron-dot-cloud are galaxies >The TV news shone a spotlight on Alzheimers yesterday by saying there >are two different [quoted text clipped - 4 lines] >short variety. I tried looking up this new research but was unable to >find it. That probably refers to the length of the peptide that is cut by the various secretases. I don't have details at hand, and offhand don't know any new story. Look at anything on AB processing, and you will find various length peptides discussed. Indeed, one of them is the key problem. bob > >The TV news shone a spotlight on Alzheimers yesterday by saying there > >are two different [quoted text clipped - 12 lines] > > bob Your right-- it is not a new story but at least a 4 year old story: > Newsgroups: sci.med, sci.chem, sci.bio.technology > From: a_pluton...@hotmail.com (Archimedes Plutonium) > Date: 11 Mar 2004 21:52:50 -0800 > Local: Fri, Mar 12 2004 12:52 am > Subject: Solving Alzheimers/Parkinsons/Prion diseases; Files150& > 151 of www.iw.net/~a_plutonium (snipped everything except this) > news from > Alzheimers from a PBS TV show in that the plaque buildup (much > like prion buildup) is > caused by a rogue scissors that wrongly snips the APP protein I was fooled by the TV station talking about these two beta amyloid as if it were hot-off the press new news when in fact they were talking about old news of at least 4 years old. So, Bob, is the scissors formally called "secretase"? Has anyone completely mapped the APP scissors? I would bet that given a normal APP scissors when introduced to some mercury compounds the scissors becomes corrupted and starts to snipping APP to where it starts the Alzheimers disease. So has anyone taken a batch of normal APP scissors, subjected it to some mercury compounds and observed whether Alzheimers is generated? What would mercury attack in a scissors? The hydrogen bonds? Or would it attack metal ions? Also, whether there is a scissors involved in Prion and Parkinson's diseases. Does mercury have that sort of property trait where it comes in contact with a scissors (secretase molecule?) and goes to corrupting it and then spins away and corrupts more scissors on down the line. Sort of like a catalyst reaction. Does mercury every behave as a catalyst? And as a catalyst on scissors? Now in Autism, if my memory is holding up, that some nerves in the infant's brain are never wired. So could there be a scissors involved in Autism? Where the infant intakes a dose of mercury such as in the thimerosal (spelling?) and where that mercury then corrupts some scissors which then cuts the wiring of a organ of the brain which then leads to Autism. Now Autism is a spectrum disease where there are all grades and gradations of Autism from severe to mild forms. This would make sense if the mercury corrupted few scissors leading to mild- Autism and where the mercury dosage corrupted a whole lot of scissors leading to severe Autism. And if I remember correctly that boys mature differently than girls, so that maybe the prescence of scissors is different at different ages between boys and girls, leading to a higher rates of Autism between boys and girls. Medical science has come a long way since the Middle Ages, but in the case of our knowledge of how mercury ruins and corrupts molecules of life, we know very little. Archimedes Plutonium www.iw.net/~a_plutonium whole entire Universe is just one big atom where dots of the electron-dot-cloud are galaxies I am glad Bob brought up secretase for it replaces the word "scissors" although scissors is so much more functional of a term. I looked up secretase to see if a structure was available and Wikipedia has a picture: --- quoting Wikipedia on secretase --- The structure of the three secretases varies widely. * The α-secretase gene has not been conclusively identified but is believed to be a metalloproteinase. * BACE is a transmembrane protein with an extracellular aspartic acid protease domain. * γ-secretase is actually a protein complex containing presenilin, nicastrin, ACH-1, and PEN-2. Presenilin is believed to harbor the protease domain and represents an important example of a rare type of protease that cleaves targets within the cell membrane. --- end quoting --- Doing some searching around, I find the metalloproteinase has a zinc ion backbone. Now I wonder how mercury or mercury compounds such as mercury-fluoride reacts with a metalloproteinase with its zinc ion? Would mercury alter the configuration of the secretase or and would it alter some of the hydrogen bonds? What exactly would mercury do to these secretases? I reckon that the mercury would act as some form of catalyst where it corrupts many of the secretase molecules. Now some people are going to say that mercury of thimerosal, the mercury preservative used in vaccines for infants and is speculated to be the blame and cause of Autism. But one must also bear in mind that with Global Warming and the huge amount of mercury thrown into the air we breathe, all around the world by coal fired power stations emits a huge amount of particle mercury. So that the mercury in coal plants in China float around the world in the air and a danger not only to the Chinese nearby but float around the world that people in the USA can end up breathing mercury produced half way round the world. So my point is that although thimerosal mercury was discontinued, the pervading fact of the world situation is that mercury in the air that we breathe has been steadily rising and increasing ever since the 20th century and it would be instructive for someone to run a statistical analysis of the amount of mercury in the air from 1950 on to 2008 correlated with the rise in the incidents of these five diseases of Autism, Alzheimers, Prion, Parkinsons, and Schizophrenia. The mercury polluted air that humanity has been breathing from 1950 onwards, I bet is a direct correlation with the increase of those 5 diseases. A case in point is that in the USA alone that the incidents of those 5 diseases are the highest in the most mercury laden air of the states of Utah and Texas. Not only do we have Global Warming from all the dirt we put in the air, but we have Global Mercury Pollution, where the coal plants in China can affect the people in the USA and where the coal plants in the USA can affect the health of people in China. It does no good for the people in the USA dept of health to proclaim that Thimerosal was safe since there is no person in this world that can ever say "mercury is safe" no matter in what dosage. Mercury is a poison, and no scientist in this world should ever side with an outfit that says mercury is safe. They should be instantly stripped of their science credentials. No person, especially infants should have ever been subjected to mercury. And as for those who claim that when Thimerosal was discontinued yet the rise of Autism continued, well, they do not realize that the rise of mercury in the air we breathe has risen unabated for the past 50 years or more. What the USA dept of health should be doing instead of defending their indefensible thimerosal is to measure how much mercury is in the air we breathe. There is a lack of study and research as to the amount of mercury in the air we breathe. Some have measured the air mercury near coal power plants but the USA should have measured the mercury throughout the USA. Now I keep harping about mercury fluoride because I have personally seen some Alzheimers cases and I know they drank fluoride water throughout there lives. The rising presence of so much fluoride in the water parallels the rise in these five diseases. So I think there maybe some connection with fluoride and mercury and these 5 diseases. Archimedes Plutonium www.iw.net/~a_plutonium whole entire Universe is just one big atom where dots of the electron-dot-cloud are galaxies (snipped) > Now I wonder how mercury or mercury compounds such as mercury-fluoride > reacts with [quoted text clipped - 6 lines] > as some form of catalyst where it corrupts many of the secretase > molecules. I find the above the ultimate irony of Prion disease, where in the 20th century, errant-thinkers thought it was one Prion molecule changing other prion molecules. Ironic, because it is likely to turn out that mercury in some special compound such as mercury-cesium or mercury-rubidium that goes around acting as a catalyst that changes the configuration of "good prions" into that of diseased prions. It was never that prions changed other prions. It was that there existed mercury along with the prions that caused the disease. And as I so long debated the facts-- the important fact that to sterilize prion disease requires enormous heat of incineration, and that heat corresponds to getting rid of mercury compounds. The reason that Prion disease seems to be in the soil is because mercury compounds are in the soil. So when the first cases of Prion emerged in the 20th century in Papua New Guinea, it was not that they were cannibilism ritual ceremony of eating the brains of deceased and transfering rogue proteins that caused Kuru, it was the mercury in the brains that was being transferred. Archimedes Plutonium www.iw.net/~a_plutonium whole entire Universe is just one big atom where dots of the electron-dot-cloud are galaxies >The TV news shone a spotlight on Alzheimers yesterday by saying there >are two different [quoted text clipped - 4 lines] >short variety. I tried looking up this new research but was unable to >find it. Now I see... This is probably on what you saw: http://www.philly.com/philly/news/nation_world/20080623_Alzheimer_s_study_yields _another_clue.html It refers to a new paper in Nature Genetics. I have just glanced at that paper. Seems that the key new finding is that the dimeric form of the AB peptide is the active form. I have not read enough of it to have much opinion on that finding, but there certainly has been a trend toward recognizing that some small soluble form is active, not the prominent insoluble plaque form. That is, the plaques per se are probably a side effect, not a cause. They are "active" only to the extent that soluble pieces come off. (This is probably true also for prions.) It is certainly plausible that the specific finding about the dimer is an idiosyncrasy of their experimental system. bob (snip) > Now I see... > [quoted text clipped - 14 lines] > > bob Okay, thanks, but I am still puzzled as to why that should be new news when the 4 year ago Alzheimers program on PBS announced that the scissors cuts the APP and it is the active cause of Alzheimers. So it seems to me that this is just a restatement of the 4 year old statement. --- quoting a passage in the above website reference --- But the two-molecule form of soluble beta-amyloid produced characteristics of Alzheimer's in the rats, they reported. --- end quoting --- Now they go on to question why this dimer form of beta-amyloid is the cause of Alzheimers yet the other forms are side-effect. I want to ask a question here myself. If mercury causes Alzheimer then a simple corruption of the scissors that cuts APP would be the cause. In this view, the mercury molecule would transit around corrupting alot of the scissors. Now, maybe the mercury molecule harbors in the dimer beta-amyloid or becomes somewhat attached to the dimer and not the other forms of beta-amyloid. I have to look to see what differences there are with the dimer versus the other beta-amyloid and whether this dimer is a mercury harbor. So it is not the dimer that causes Alzheimers but the mercury and it seems to attach to the dimer. And the mechanism of causation would be that the mercury corrupts the scissors which produces unwanted garbage plaque. Now in Prion disease, the mercury is probably in a different compound and may not be harbored in other proteins, and where the Prion onset is due to the mercury coming into contact with disease free prions and misshappening them into plaque-prion. Has anyone actually analyzed how much mercury and mercury compounds were inside the heads of Prion and Alzheimers deceased? Perhaps that is the biggest question of all. If all Alzheimers and Prion deaths have a high number of specific mercury compounds such as mercury-cesium or mercury-fluoride, then we may have the road to the final answers as to what causes these diseases. Archimedes Plutonium www.iw.net/~a_plutonium whole entire Universe is just one big atom where dots of the electron-dot-cloud are galaxies plutonium.archime...@gmail.com wrote: > (snip) > > [quoted text clipped - 16 lines] > > > > bob I did some searching around for whether the dimer has some affinity for mercury compounds. Found the function of all these AB peptides as waste removal to the spinal fluid. The dimer form especially carries the mercury compounds and railroad hauls them off to the spinal fluid. So I wonder when they transfered the active dimer to rats, whether they were transferring the mercury compounds also. So did the above study run the dimers through a mass spectrometer to see if they transferred mercury compounds? One report in my search spoke of Alzheimers having higher levels of both mercury and bromine. I am not sure how mercury combines in compounds. My sense of the situation is that mercury moves mostly in ion form without bonding into a molecule. And that mercury has that sort of "alloying affect" when near metal ions. Perhaps that alloying affect is what misshappens the APP scissors and corrupts it, and ditto in Prion disease, where it is the mercury that misshapes the normal prions. Now another question is why would a person in older age succumb to Prion disease instead of Alzhiemers or vice versa when both are caused by mercury presence? And the only answer that seems reasonable is that the mercury is compounded differently. That mercury with fluoride maybe the Alzheimers path and that mercury with cesium or rubidium maybe the prion path. Now there is well known cases of rapid progression for both Alzheimers and Prion, and this would make common sense as to the amount of mercury in the brain. So if there is alot of mercury then you have the rapid progression disease. Also, I want to note as to why England has so much prion in sheep scrapie. Mercury is very much present in England especially with all the coal burning. But could it also be a human factor for why England has so much sheep scrapie? Could it be that something like thermometers used to measure the sheep. Or something of mercury used as pesticide or herbicide in England going back centuries? As far as I know, the world's worst outbreaks of prion disease were in England and in the Rocky Moutains of Colorado on deer or deer related animals. The Colorado incident has a high concentration of cesium or rubidium along with mercury. So if mercury is the culprit of these 5 diseases, we should expect clusters of cases in different spots of the globe, where a abnormal concentration of mercury compounds was in the environment. And this is very much the case so far. Archimedes Plutonium www.iw.net/~a_plutonium whole entire Universe is just one big atom where dots of the electron-dot-cloud are galaxies I notice there is a nice grouping of these 5 diseases as per age of attack: Autism in infants before age 10 Schizophrenia in boys as teenagers and girls in 20s Alzheimers Parkinsons Prion in old age So we have almost every age group represented except for maybe 30s to 50s. So does the age grouping match the idea of mercury poisoning? I would say so, because mercury can be an accumulative affect and so most are old age diseases. And as for Autism, a large dosage of mercury can damage brain sheaths from developing. Now I spent a long time considering different compounds of mercury to explain the different 5 diseases, so that say prion was mercury cesium whereas Alzheimers was mercury fluoride. That may have been the wrong approach. Perhaps a better approach would have been to focus on the metal ions in the proteins under attack in the disease, or to focus on what metals the proteins bind. In Alzheimers, instead of wondering what the mercury compound is such as mercury rubidium, instead, focus on what metal ions constitute the APP scissors and the protein that is cut. If zinc ions are involved in Parkinsons alpha synuclein and zinc and copper in amyloids of Alzheimers and copper and manganese for Prion proteins. Then I should not worry so much as what form of mercury is involved, for the concern is that mercury acts differently on zinc ions than on copper ions. So if the reaction of mercury to copper ions is different than the reaction of mercury on zinc ions then we can explain why prion disease is different than Alzheimers disease, for the one is mercury attacking the zinc ions in Alzheimers and mercury attacking the copper ions in Prion. Whereas before I was focused on mercury-cesium versus mercury-fluoride as the difference between prion and Alzheimers. In the end, it may well be both the type of mercury and the type of metal ion in the protein. One other note is that there has never been a case where a person contracted any two or three of the three old age diseases of Parkinsons, Prion and Alzheimers. I know of no case where a person had say Parkinsons and then also had Alzheimers. Now this may or may not support this theory of mercury as the cause, because one would think that if mercury is the poison cause that in some people the mercury would set up two or more of these diseases simultaneously. And perhaps even see cases of Autistic children starting to have Alzheimers or Parkinsons. Now maybe there are such cases but have not been reported. And maybe there are many such cases but one of the diseases takes over and masks the presence of the other disease and noone bothered to autopsy for 2 or more diseases simultaneously. Now in the case of Schizophrenia we have dopamine blockage and perhaps zinc ions as substitute for dopamine. So Schizophrenia is much similar to Parkinsons in that dopamine is reduced. And where Prion and Alzheimers are very much alike in the fact that a protein garbage dump is set up in the brain which kills. So in Autism, Schizophrenia and Parkinsons we have things "missing in the brain" whereas in Prion and Alzheimers we have garbage accumulation strangulation. So the mercury maybe all the same in all these 5 diseases where it could be ethyl mercury. But I rather suspect it is mercury compounds that facilates the onslaught of these 5 different diseases. Archimedes Plutonium www.iw.net/~a_plutonium whole entire Universe is just one big atom where dots of the electron-dot-cloud are galaxies Archimedes Plutonium wrote: > One other note is that there has never been a case where a person > contracted any two or three [quoted text clipped - 12 lines] > the other disease and noone bothered to autopsy for 2 or more diseases > simultaneously. Maybe there is some evidence of these simultaneous multiple mixes. There is evidence that Prion disease comes in a plethora variety and where some prion proteins are gradations from a set standard. So the variety of diseased proteins in prion disease could be the fact that the person has both Alzheimers along with CJD or some Prion disease simultaneously. And, if I am not mistaken, there is evidence in Parkinsons disease of the forgetfullness found in Alzheimers. It would be that the Parkinsons shaking would mask the Alzheimers loss of memory. And also, let me comment on the old and decrepit idea that these diseases are genetic based. The genetic base flys out the window with a mercury poisoning causation, because mercury can be an accumulative poison just like lead poisoning would be that the surroundings of the individual are family members and so where one of the family is in increasing exposure to mercury buildup, all the members of the family are likely to have increasing exposure to the mercury. No doubt some genetics plays a role in these 5 diseases such as whether the genetics of the proteins to clean out the body of mercury present, would play a factor in who in the family gets these diseases. But old medical ideas on these 5 diseases placed too much emphasis on genetics when genetics has little importance to the fact that mercury is a poison. Mercury as a poison is not a genetics issue. The thing we have to remember is the big picture of these diseases for the last 2,000 years of history. All five of these diseases were either unknown or rare before 1901. Only in the 20th century do these five diseases really emerge to prominence, especially Autism and Alzheimers. So a commonsense reasonable person would ask what has changed by 1901 that was so different than the preceding 1899 years? The answer to me is that our increasing industrial air pollution of the modern times where mercury becomes available to be breathed in by every person no matter where they reside on the globe. That the coal fired electric power stations in USA and China and have mercury drift into the air and be breathed in by any person in any country of the world. By the way, I found out that scientists deem the South Pole upwind is the cleanest oxygen air in the entire globe. But my point is that the rise of these 5 diseases starting about 1901 parallels the rise of mercury in the air that every person on the globe cannot escape breathing. We have had other pathways of increasing contact with mercury such as teeth fillings in dentistry and such as the thimerosal in baby vaccines. But the biggest culprit of making mercury inescapable for every living and breathing human is the mercury we put in the air by burning coal and other petrol products such as oil refineries. With the increasing dirty and mercury laden air of the globe, so has risen the incidence of these 5 diseases. Archimedes Plutonium www.iw.net/~a_plutonium whole entire Universe is just one big atom where dots of the electron-dot-cloud are galaxies >>http://www.philly.com/philly/news/nation_world/20080623_Alzheimer_s_study_yields _another_clue.html >> [quoted text clipped - 18 lines] >this is just >a restatement of the 4 year old statement. Seems that you have completely misunderstood what I wrote above, and what the news story says. It has absolutely nothing to do with what you are talking about above. The key point here is showing that the dimer is the active form of AB. This is "completely" new info -- very exciting. It has nothing to do with anything you talk about above. bob > Seems that you have completely misunderstood what I wrote above, and > what the news story says. It has absolutely nothing to do with what [quoted text clipped - 3 lines] > > bob Kindly explain to me what the difference is between the AB dimer and the APP and APP scissors with resultant stub. Granted I have stretched myself thin by being involved with so many sciences and not just this topic alone and for me to jump around and come back to this topic, and my increasing old age of approaching 58, that I need these recaps. In the APP scissors stub, according to PBS, is the beta amyloid that collects as plaques. The AB is the beta amyloid plaque also. So, as far as I can see APP stub = AB dimer If that is not true, Bob, then please explain what I am missing. Archimedes Plutonium www.iw.net/~a_plutonium whole entire Universe is just one big atom where dots of the electron-dot-cloud are galaxies >> Seems that you have completely misunderstood what I wrote above, and >> what the news story says. It has absolutely nothing to do with what [quoted text clipped - 6 lines] >Kindly explain to me what the difference is between the AB dimer and >the APP and APP scissors with resultant stub. (Quotes are from the original press release at Harvard.) "Alzheimer's disease is marked by the build-up of plaques consisting of beta-amyloid protein fragments, ..." The "beta-amyloid protein fragments" are made by cutting from the original gene product (the APP). I called the fragments AB (as in amyloid beta). There is sometimes a number with it, such as 40 or 42. One of those is the key length; I can't remember which, but they used the right one. "The extracts contained soluble one-molecule (monomer), two-molecule (dimer), three-molecule (trimer) or larger aggregates of beta-amyloid, as well as insoluble plaque cores." bob > The AB is the beta amyloid plaque also. The AB is IN the plaque. >So, as far as I can see >APP stub = AB dimer Don't know want you mean by stub. AB is what the enzymes produce; it is active in dimeric form. bob (snipped) > (Quotes are from the original press release at Harvard.) > [quoted text clipped - 25 lines] > > bob Thanks for the information, then there are 3 stubs of the APP, or what you call fragments. Now I do not know why they are elated in finding the dimer as active. As far as I can see, who cares, since the mechanism of the Alzheimers is the fact that the scissors is rogue and makes those bad cuts leaving 3 fragments. So why fuss over analysis of the fragments, for it seems logical to me that the scissors is malfunction and so I would focus on why the scissors makes bad cuts. And I would guess it does so because some form of mercury is present. Of course we need the knowledge of everything involved, but it seems diligent to focus mainly on why the scissors went awry, making cuts of fragments. Bob, do they mention what metals form the dimer structure? And while your at it, can you tell me what metals are in the scissors ( I believe you call them secretases). Now I would think it very valuable to make a table in which we have Alzheimers and Prion and where we list all the proteins and protein framents and all the metal ions within their structure, and then make a list of all the secretases and the metal ions inside them. I think such a table would show us some very parallel features, so that a mercury poison could account for the diseases in that it alters the secretases in Alzheimers and alters the prion proteins in Prion. Does it say there in the article whether the metal ions in the Alzheimers fragments all have zinc whereas the metal ions in the secretases have copper? And jumping over to Prion, do the proteins have copper ions? I am wondering if mercury alloys with say the copper ion and as the secretase cuts the APP, then the mercury-copper alloy causes a malfunction and makes fragments. Constrasting that with Prion where the mercury alloys with the copper and whenever this alloyed protein comes in contact with a normal prion molecule, it causes the bending to be a diseased prion protein. Bob, now I understand that a mass spectrometer of any various brain tissue is going to show up some atoms of mercury. But I wonder if anyone has purified the disease agent of Prion to a high purity and then a second batch of normal prions in high purity, and then whether they ran a mass spectrometer to see if the disease batch contains atoms of mercury whereas the normal batch is mercury free? And I know that no-one has ever reported a case of catching Alzheimers from a inflicted person, but if mercury is the cause, then like Prion, if the brain tissue is eaten then another person can catch it. So I wonder if anyone has done a mass spectrometer of the secretases of a normal person versus an Alzheimers. Some reports claim a higher concentration of mercury in Alzheimers, but can we focus that to the secretases in particular, or find out if some regions have the highest mercury concentration. And also the rarity of Prion disease compared to the frequency of Alzheimers would make sense in that Alzheimers has copper in the secretase and so they are corrupted and Prion has copper in the normal prion. So the rarity correlates to where the copper ions are placed. What irritates me out of this whole thing is that we could have run extensive mass spectrometers for the presence of mercury, but somehow we never managed to research heavy metals in the brain. P.S. now in Autism, the diseased region seems to be a lack of growth of nerve sheaths. So here I wonder if mercury in an infant is attracted most by a region in the infant's brain where the highest concentration of copper ions is the sheath area? There are copper ions throughout the infant's brain, but I wonder if the sheath area is especially vulnerable to mercury? Archimedes Plutonium www.iw.net/~a_plutonium whole entire Universe is just one big atom where dots of the electron-dot-cloud are galaxies On page 359 of Introduction to Genetic Analysis, by Griffiths, Miller, Suzuki, Lewontin, Gelbart, 1996 is a page that shows a picture of the normal PrP and then a picture of what happens to turn that normal PrP into scrapie disease. The normal PrP has two helices, but in the diseased form, those two helices have been changed into 4 beta sheets as the picture in the textbook shows. Now, the theory of metal causation as mercury with the likely suspect, one simply has to ask some chemistry questions. If we place normal PrP into solution of several compounds of mercury does not the mercury when in contact with PrP change 2 helices into 4 beta sheets? Likewise for Alzheimers disease, although I have no book that shows a picture of the 3 fragments of beta-amyloid that the APP secretases (scissors) cuts. But if we had in solution, normal APP and normal secretases and then applied some mercury compounds, perhaps mercury-fluoride, does not that reaction end up drastically changing the normal APP into beta sheet fragments that cause Alzheimers disease? The similarity is striking in that the endproduct in Prion and the end product in Alzheimers are proteins that our bodies cannot remove. They are unremovable as plaques becuase they were formed by a poison of mercury and which the animal bodies have not evolved a trash removal system since these diseases are the increasing amount of mercury poisons present in modern day air we breathe. Chemists who are specialists in the mercury molecules, perhaps can easily spot how a mercury compound can alter helices into beta sheets. It must not take much energy because in the 1990s with the phony-Prusiner model, the energy to make that alteration was ascribed not to mercury compounds but to a look-alike folded PrP molecule. So if a close resembling PrP was thought to be the culprit in the 1990s, it had little energy wise difference from the normal PrP, which suggests that a mercury compound as the true culprit, would easily substitute as the catalytic converter of helices into beta sheets. So if there is a chemist out there, expert in how mercury acts as a catalyst in conversion of helices to beta sheets and takes a look at the normal PrP versus diseased PrP and takes a look at normal APP and scissors versus Alzheimer diseased APP and scissors, that I am quite confident they can immediately select a mercury compound poison that is the true culprit of these diseases. Archimedes Plutonium www.iw.net/~a_plutonium whole entire Universe is just one big atom where dots of the electron-dot-cloud are galaxies Maybe I can throw a few ideas in here as to the significance of this work. I've had a quick scan through of the Nature Medicine paper - Amyloid-bold beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory - (http://www.nature.com/nm/journal/vaop/ncurrent/full/nm1782.html), and what they are saying is that the dimers (two molecules joined together) of the amyloid beta (AB) fragment is the active agent in Alzheimer's disease. The reason this is interesting is that for a long time there has been a debate over the significance of the plaques (large clumps of AB) in Alzheimer's disease. Some people have thought that they are responsible for killing cells, some others have said that they are actually protecting cells, by mopping up the more deadly soluble fragments of AB. The Amyloid Precursor Protein (APP) sits in the membrane of cells, and is cleaved (cut up) by several different enzymes. This creates a fragment that is outside the cell, and one that is fixed in the membrane. However, it also creates this very small fragment, AB, which contains just a few amino acid building blocks. If that AB fragment is cut so that it has a few more amino acids than normal (42 compared to 40, say) it becomes sticky, and adheres to itself. This forms the plaques that are seen in brain slices from patients. What this paper is saying is that two AB molecules stuck together (the dimer) is able to damage nerve cells. Adding the dimer to cells in culture causes a reduction in long term potentiation (LTP), which is thought to be part of the basis of learning and memory, obviously of interest in Alzheimer's studies. Archimedes Plutonium wrote: As far as I can see, who cares, since the mechanism of the Alzheimers is the fact that the scissors is rogue and makes those bad cuts leaving 3 fragments. So why fuss over analysis of the fragments, for it seems logical to me that the scissors is malfunction and so I would focus on why the scissors makes bad cuts Attempts have been made to target the 'scissors', but unfortunately these proteins are involved in a signalling process called Notch signalling, which is vitally important in process such as cell fate and cell division, so blunting the scissors is a very tricky process. If however, one can target the AB dimer, this has no known positive roles, and so is a much better drug target. Also, knowing the dimer is important in the disease shows that attempts to break up the plaques are likely to be counterproductive, as this would release more of the dimer, so causing more damage. What the authors of the paper also do is identify specific protein targets that are affected by the AB dimer. This gives a further target for theraputic intervention, as it might be possible to block the negative effects of the AB dimer not by targeting it directly, but by stopping it from interacting with other proteins. This is a very different disease process to that of prion disease, where the prion protein switches between two forms (one of which is toxic), and where the toxic form promotes the conversion of the non- toxic form into the toxic. I do not know what role mercury might play in either of these topics. >Maybe I can throw a few ideas in here as to the significance of this >work. They will make no difference. AP is right; the rest of the world is wrong. On Jul 1, 5:33 pm, david.bostw...@chemistry.gatech.edu (David Bostwick) wrote: > In article <eb9f12c1-34b4-4f64-b1a5-7a37674cb...@d77g2000hsb.googlegroups.com>, Andrew Porter <andrew.port...@googlemail.com> wrote: > > >Maybe I can throw a few ideas in here as to the significance of this > >work. > > They will make no difference. AP is right; the rest of the world is wrong. Can you explain which what you mean by 'they will make no difference' please? >On Jul 1, 5:33=A0pm, david.bostw...@chemistry.gatech.edu (David >Bostwick) wrote: [quoted text clipped - 9 lines] >Can you explain which what you mean by 'they will make no difference' >please? "They" refers back to "a few ideas." > Maybe I can throw a few ideas in here as to the significance of this > work. [quoted text clipped - 61 lines] > toxic form into the toxic. I do not know what role mercury might play > in either of these topics. Thank you very much, very much indeed for the clarity of your post, for you certainly made it clear to me the value of the AB dimer. Note: in the above, my comments are not segregated out from Mr. Porter's comments, but the reader should be able to separate them out. Andrew, I am at this search in Alzheimers and Prion not for drug remedy but solely for knowledge of how the disease works. And this AB dimer certainly is further knowledge, but I hope the medical research labs focus more on the "scissors" because the disease is further upstream than the sticky AB dimer. I hope the research labs focus on why the scissors of APP gets corrupted. Why and how that scissors makes those gone-awry cuts. Because this scissors is the cause of Alzheimers and the AB dimer is simply a aftereffect. There maybe some drugs to target the AB dimer, but that is only a bandage for Alzheimers if it is the scissors that creates the AB dimer in the first place. I think the most prudent course of action is to focus on the scissors and how it becomes rogue. Is it a chemical poison like mercury that makes the scissors rogue? I think that our research should focus on those questions. Thanks again for explaining the AB dimer. Archimedes Plutonium www.iw.net/~a_plutonium whole entire Universe is just one big atom where dots of the electron-dot-cloud are galaxies Just quick and general... Porter's post was excellent. A new person, one with knowledge, took the time to write more than most of will do. Diseases have many steps. One goal is to simply try to identify and understand them. Treating a disease may occur at any of several levels. Practical considerations are involved. Be assured there is much work going on to try to understand and deal with the secretases, but it is difficult. bob >> Maybe I can throw a few ideas in here as to the significance of this >> work. > Just quick and general... > > Porter's post was excellent. A new person, one with knowledge, took > the time to write more than most of will do. Excellent post, indeed. > Diseases have many steps. > [quoted text clipped - 5 lines] > > bob Well I do not like that methodology of looking for treatments at several levels, for it looks as though time and money are thrown away, until the actual cause of the disease is found and then plot a course to treatment. Suppose they find some drug to lessen the AB stickyness. The scissors still churns out more of the plaque. So if they spend all the time and money on finding the real cause, suppose it is mercury fluoride that produces minute amounts of hydrofluoric acid that cause some bonds in the secretase to misshappen and then cause the rogue cuts. Suppose it is these two chemicals of mercury and fluoride. Then the ultimate treatment is to get rid of fluoride in the drinking water and to cut down on the body intake of mercury from the environment. And thus, all the drugs in the meantime were sort of useless. And if they spent the time and money focused on the real cause, that could be found faster than if they parcelled time and money for intermediate treatment. And perhaps a real cure would be some chemical that goes into the head and removes the mercury and fluoride. The rise of diseases of Alzheimers and Prion and Autism and Parkinsons and Schizophrenia seem to parallel the rise of the increasing prescence of fluoride in water and mercury intake. Tell me something Bob, why is it that when mercury is ingested or breathed in that it seems to zoom towards the head region and seems to set up shop in the head organs? Why the head? Is it because of the electrical environment of the head? Maybe the head is nothing special but that it stays in the head longer than if in other parts of the body? Another question about the 2 helices in Prion that are altered into 4 beta sheets. Is there a radioactive element, say cesium or rubidium or radon that are the best elements to convert helices into beta sheets? We heard a story out of England and Russia of a poisoning with radioactive polonium where just a tiny amount kills. So I wonder if a tiny amount of some radioactive element, when it enters the head, and as it comes into contact with say helices, almost instantly can convert those into beta sheets. Now I do not know the configuration of the APP scissors whether it is a far larger molecule than PrP in Prion. Whether the APP scissors even has helices or whether it even has metal ions such as copper or zinc in its configuration. But if a radioactive element were present in the head and comes in contact with a APP scissors, whether it can instantly change the configuration and thus cause the plaque fragments to occur in each cut. What I am fishing for, is a chemical element or compound which when in contact with 2 helices, almost instantly changes them into 4 beta sheets. Does it require mercury? Alot of Prion disease occurs in deer family of animals around Colorado. There is plenty of mercury there, but it sounds as though some other element is the contributing cause. England has a high rate of Prion disease so what elements are found in the English countryside? There is alot of coal in England so mercury is plentiful, but is there some radioactive element such as found in Colorado? An easy research would simply be to run mass spectroscopy on the brains of Prion and Alzheimers hoping to find the "poison molecules" I do not know what elements would implicate Schizophrenia. As for Parkinsons, it is most dense in farm communities. In farm communities alot of water comes from deep wells and some mercury is used in agriculture such as seed coating or as fungicide. So it is rather easy to visualize how mercury can get into a well water. Also, alot of farms have there trash buried in a deep pit and perhaps mercury from thermometers or used electrical equipement is thrown into this trash pit which leeches into the well water. So I think the very best course of action of research would be to draw the normal proteins of Prion and Alzheimers and then draw the diseased proteins and then ask the question, what chemical poison can turn the normal molecule into the disease molecule. What can alter PrP of 2 helices into 4 beta sheets? Find what chemical candidates do that. If they find that say Cesium-Mercury easily converts 2 helices into 4 beta sheets, then we are arrived at the solution of the disease. Do the same for Alzheimers. These diseases that have altered proteins are easier to solve than diseases of "something missing in the brain" such as Autism where there are missing connective sheaths. Here we have to find how sheaths are formed normally and then find why they are not formed and what chemical poison is preventing that formation. Archimedes Plutonium www.iw.net/~a_plutonium whole entire Universe is just one big atom where dots of the electron-dot-cloud are galaxies I did a Google search with these terms "mercury helices beta sheets" and found these instructive: [DOC] Problem of Focus: File Format: Microsoft Word - View as HTML The protein has two alpha helices, one beta sheet and a variety of areas that undergo structural dynamics. The mercury binding site is located between the ... www.clarkson.edu/honors/research/papers/Worczak-Marianna.doc - Similar pages - Note this structure model of mercury binding protein Because of their affinity to sulfhydryl groups mercury ions are toxic ... beta sheet and two alpha helices in contact with the sheet (alpha-beta sandwich) . ... www.biologie.uni-hamburg.de/lehre/bza/kanal/transp/merp/emerpm.htm - 1k - Cached - Similar pages - Note this Protein unfolding at interfaces: Slow dynamics of [alpha]-helix to ... and the helices fluctuate rapidly. The protein then adopts ..... vibrational CD for model peptide and protein beta-sheets. J Am ... doi.wiley.com/10.1002/prot.20183 - Similar pages - Note this [DOC] A study of bacterial detoxification system for mercury File Format: Microsoft Word - View as HTML UCSF Chimera beta version 1 build 2199 win 32 platform (Pettersen et al., ... Structure of merP protein (a helices: 2; b sheet apparently three-stranded) ... www.dbbtcoc.edu.in/Bact_mercury.doc - Similar pages - Note this Structure of human biliverdin IX<img border="0" src="/__chars/beta ... -helix F. The central beta -sheet and the two groups of helices are held .... in the crystal derivatized by the binding of a mercury atom to Cys 109, ... www.nature.com/nsmb/journal/v8/n3/full/nsb0301_215.html - Similar pages - Note this 1H NMR studies of the mercuric ion binding protein MerP ... The protein folds into an antiparallel beta-sheet, beta 2 beta 3 beta 1 beta 4, with the two antiparallel helices on one side of the sheet. ... www.ncbi.nlm.nih.gov/pubmed/8111228 - Similar pages - Note this (IUCr) Structure determination of the O-methyltransferase NovP ... The mercury-derivative data set was collected in-house to 2.45 Å resolution .... -helices and seven [beta] -strands were placed in this way and optimized by ... scripts.iucr.org/cgi-bin/paper?dz5108 - Similar pages - Note this Structure determination of a mercury binding protein, MerP Bacteria with plasmids encoding the mercury detoxification system have the ... the two $/alpha$ helices overlaying a four strand antiparallel $/beta$ sheet. ... repository.upenn.edu/dissertations/AAI9713009/ - 12k - Cached - Similar pages - Note this Now what I wonder, is whether a normal PrP molecule can have its metal ion of zinc or copper missing and replaced by mercury? And this mercurial PrP is the disease causing agent. Likewise in Alzheimers, I wonder if the APP secretases (scissors) had a copper or zinc ion replaced by a mercury ion and thus was causing rogue cuts. Has anyone purified the diseased PrP and the APP secretases and run a mass spectroscopy for the presence of mercuy ions? Archimedes Plutonium www.iw.net/~a_plutonium whole entire Universe is just one big atom where dots of the electron-dot-cloud are galaxies On Jul 2, 8:26 am, plutonium.archime...@gmail.com wrote: > I did a Google search with these terms "mercury helices beta sheets" > and found these > instructive: Some basic biology. Proteins are composed of chains of amino acids. There are 20 in common usage, and each protein contains one chain of amino acids joined end to end. This is called the Primary Structure. Certain combinations of amino acids will attempt to fold together to make a more thermodynamically stable structure, for instance by protecting fatty, organic chemical groups from contact with water. The two most common folds are called Alpha Helices (which look like a minature spiral staircase, with each rise of the stair a different amino acid) and Beta Sheets (formed where two or more parts of the protein fold back on each other.) These are termed Secondary Structure. The final level of organisation, Tertiary Structure, is the 3D shape of the protein as a whole. For instance, a group of four Alpha Helices may bunch together to make a bundle in the middle of the protein. @Plutonium So the search you did for "mercury helices beta sheets" is like searching for "Shakespeare Paper Pen". This is why you have pulled out someone's thesis proposal on making a biosensor for detecting mercury, and a bunch of references to a bacterial protein that binds mercury, none of which sheds much light on the topic. A better search would be 'prion protein mercury', or 'alzheimers disease mercury / APP amyloid mercury'. Either of these shows that there has been some interest in investigating whether mercury is involved in either disease. However, searching for other heavy metals with these diseases also pulls out a large number of hits. Earlier, you said: "Well I do not like that methodology of looking for treatments at several levels, for it looks as though time and money are thrown away, until the actual cause of the disease is found...Suppose it is these two chemicals of mercury and fluoride. Then the ultimate treatment is to get rid of fluoride in the drinking water and to cut down on the body intake of mercury from the environment...And thus, all the drugs in the meantime were sort of useless. And if they spent the time and money focused on the real cause, that could be found faster than if they parcelled time and money for intermediate treatment. " The point here is that you assume we already know what the real cause of diseases such as Alzheimer's disease (AD) is. This is an issue on several levels. First, we do have a good idea of some of the components of the disease - such as the amyloid beta (AB) protein - and we know where this comes from (processing of the APP protein.) What we don't always know is what the trigger for making the pathogenic form is. It may be a heavy metal, it may be some other enivornmental condition. It can be inherited genetically - some families carry mutations in either the APP protein or the secretase ('scissor') proteins that give them a very high incidence of early onset Alzheimer's disease. It may be that for a person who lacks these mutations and still develops AD that there were a multitude of factors that all contributed. Therefore, examining the disease process more towards the end point (e.g. reducing the toxic effects of AB) is actually a good strategy, as it will help tackle the disease whatever is causing it. Lots of investigation is ongoing into the causes; if you look on PubMed and search there you will find lots of hypotheses. It is never a good idea in science to start with an idea that is fixed - such as mercury causing all these diseases - and then look for evidence that fits what you already believe. As I say above, a heavy metal effect is not needed to account for the early onset familial forms of AD. > Has anyone purified the diseased PrP and the APP secretases and run a > mass spectroscopy for > the presence of mercuy ions? The structure of PrP has been determined by X-ray crystallography, and the metal ions which it binds have been noted. > Now what I wonder, is whether a normal PrP molecule can have its metal > ion of zinc or copper missing [quoted text clipped - 3 lines] > zinc ion replaced by a > mercury ion and thus was causing rogue cuts. Elemental mercury is a very different beast to zinc or copper, they do not bind to proteins in the same way. Therefore, mercury would not replace zinc or copper. However, a very quick search of PubMed pulled up a paper showing elevated levels of manganese in some prion protein molecules - if you could shift away from mercury you might find some very interesting other discoveries. > On Jul 2, 8:26�am, plutonium.archime...@gmail.com wrote: > > I did a Google search with these terms "mercury helices beta sheets" [quoted text clipped - 92 lines] > molecules - if you could shift away from mercury you might find some > very interesting other discoveries. Thanks, I will have to give those a search tonight. I am not stuck with "mercury" for over the past 10 years have looked at magnetic manganese and looked at aluminum and other metals. It is just that mercury is probably the culprit in at least 2 of these 5 diseases and thus is the highest suspect. My mind is not dogmatic over mercury, it is just that we have such little experimental evidence of metals in these proteins, that I can only tout the "prime suspect" which would have to be mercury for its is proven to be a poison. I would not be surprised if mercury was absent in several of these 5 diseases, but I feel confident that mercury is to blame for at least 2 of the 5 and thus the prime suspect. I do have a problem when saying that mercury is involved in all 5 of these diseases because then the spectre looms that some victim should have simultaneous diseases such as both prion and Alzheimers, or Parkinsons and Alzheimers all in one person. Mercury still maybe involved in all 5 diseases as part of a chemical chain reaction where the mercury may facilitate some "activation energy". So the prescence of a group of chemicals to start the disease where mercury ions or methyl mercury or ethyl mercury in presence of fluoride may disrupt hydrogen bonds on proteins, creating a site for hyrdofluoric acid to arise and where the hydrofluoric acid then causes the *shape changes in the protein*. So it maybe a chemical brew of metals in the prescence of proteins that is the disease agent. Andrew, I can appreciate researchers looking for drugs to treat the AB stickyness as a sort of band-aid help to Alzheimers patients. Let me offer a different analogy, of suppose a city has a sniper killer and has shot many bystander victims. And rightfully we should run to the aid of the victims to get them better, but the killing will not stop until the sniper is apprehended. The medical research community maybe found guilty of not spending more time and focus on the cause of Alzheimers rather than their greed for making drug dollars over a band-aid amelioration of Alzheimers. If Alzheimers is ultimately found to be caused by fluoride in the drinking water in conjunction with excessive mercury in the brain, then the cure for Alzheimers is take the fluoride out of the water and avoid mercury exposure. So stop drinking fluoridated water and have a drug that can get the mercury out is a cure, provided they are the cause. Archimedes Plutonium www.iw.net/~a_plutonium whole entire Universe is just one big atom where dots of the electron-dot-cloud are galaxies >> Diseases have many steps. >> [quoted text clipped - 11 lines] >actual cause >of the disease is found and then plot a course to treatment. It is not black and white, and requires some judgment. For the sake of brevity here, I will emphasize the other side. Porter already wrote about why it may be better to target the dimer -- both why targeting the scissors may not work, and why targeting the dimer may be good. A key problem is that there is no way to know until one tries it. Unintended side effects are common in drug development. That is why it is good to try different things. Note Porter's point of why targeting the dimer _may_ have fewer side effects. But we cant know until it is tried. The notion of "the" cause is a gross oversimplification. Sometimes helpful, sometimes not. "A" happens, then B, C, etc etc. Neurons die. Intervening anywhere in there may help neurons survive. It may well be that there is more than one disease pathway, and that treatments at early steps would only help some cases, whereas treatment at a later step may help different forms of the disease. That is, the disease is "neurons die", with various pathways converging at that final result. For example, we know that some cases of Alz are "due" to mutations, in one gene or another. But -- probably -- all paths end up with more dimer, which kills. And even that is only a good hypothesis for now. In some ways, focusing on one path might be good -- but not if it is the wrong one. Experts in the field argue about the allocation of resources -- with each favoring his own view. Only in retrospect do we know. bob > plutonium.archimedes@gmail.com wrote: <snip all nonsense> I first thought that the radium nut was back. Now I see that it was only Archie Poo. All materials get heavier when heated by E/c^2. Einstein pointed that out a bit more than a century ago. Bill |
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