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Andrew Porter
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 Posted: Tue Jul 01, 2008 4:02 pm Post subject: Re: #60 how mercury can turn PrP into the scrapie form ; new |
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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. |
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Andrew Porter
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| Posted: Tue Jul 01, 2008 4:47 pm Post subject: Re: #60 how mercury can turn PrP into the scrapie form ; new |
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On Jul 1, 5:33 pm, david.bostw...@chemistry.gatech.edu (David
Bostwick) wrote:
| Quote: |
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? |
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Guest
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| Posted: Tue Jul 01, 2008 5:10 pm Post subject: #61 clarification on the AB dimer and its stickyness ; new b |
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Andrew Porter wrote:
| Quote: |
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.
|
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 |
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David Bostwick
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| Posted: Tue Jul 01, 2008 9:33 pm Post subject: Re: #60 how mercury can turn PrP into the scrapie form ; new |
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In article <eb9f12c1-34b4-4f64-b1a5-7a37674cb5c9@d77g2000hsb.googlegroups.com>, Andrew Porter <andrew.porter1@googlemail.com> wrote:
| Quote: |
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. |
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David Bostwick
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| Posted: Tue Jul 01, 2008 10:51 pm Post subject: Re: #60 how mercury can turn PrP into the scrapie form ; new |
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In article <c45d1dd9-93d3-4acf-bd5c-e2deb78f8b0f@a1g2000hsb.googlegroups.com>, Andrew Porter <andrew.porter1@googlemail.com> wrote:
| Quote: |
On Jul 1, 5:33=A0pm, 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. =A0AP is right; the rest of the world is wro=
ng.
Can you explain which what you mean by 'they will make no difference'
please?
|
"They" refers back to "a few ideas." |
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Guest
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| Posted: Wed Jul 02, 2008 5:39 am Post subject: #62 what chemical is the best at changing 2 helices into 4 b |
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Bob wrote:
| Quote: |
On Tue, 1 Jul 2008 10:10:31 -0700 (PDT),
plutonium.archimedes@gmail.com wrote:
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.
| Quote: |
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
|
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 |
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| Posted: Wed Jul 02, 2008 7:26 am Post subject: #63 mercury forms the metal ion of some proteins ; new book: |
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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 |
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Bob
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| Posted: Wed Jul 02, 2008 9:03 am Post subject: Re: #61 clarification on the AB dimer and its stickyness ; n |
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On Tue, 1 Jul 2008 10:10:31 -0700 (PDT),
plutonium.archimedes@gmail.com wrote:
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
| Quote: |
Andrew Porter wrote:
Maybe I can throw a few ideas in here as to the significance of this
work. |
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Salmon Egg
Guest
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| Posted: Wed Jul 02, 2008 9:24 am Post subject: Re: #58 new news on Alzheimers as the dimer is the active in |
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In article <ajjg64140rk0nhtliinduunc25it4cv2qs@4ax.com>,
Bob <bbx107.XYZ@excite.XYZ.com> wrote:
| Quote: |
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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Andrew Porter
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| Posted: Wed Jul 02, 2008 12:23 pm Post subject: Re: #63 mercury forms the metal ion of some proteins ; new b |
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On Jul 2, 8:26 am, plutonium.archime...@gmail.com wrote:
| Quote: |
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.
| Quote: |
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.
| Quote: |
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.
|
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. |
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Guest
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| Posted: Wed Jul 02, 2008 5:16 pm Post subject: #64 mercury to blame for at least 2 of these 5 diseases ; ne |
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Andrew Porter wrote:
| Quote: |
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
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.
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.
|
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 |
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Bob
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| Posted: Thu Jul 03, 2008 9:23 am Post subject: Re: #62 what chemical is the best at changing 2 helices into |
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On Tue, 1 Jul 2008 22:39:21 -0700 (PDT),
plutonium.archimedes@gmail.com wrote:
| Quote: |
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
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.
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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 can’t 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 |
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