Friday, May 10, 2013

Parkinson Amelioration I

Parkinson Amelioration I

Andre Willers
10 May2013
This is not medical advice . Consult your health professional .
Synopsis :
Alzheimer’s , Parkinson’s and Huntingdon’s are caused by TAU proteins interacting with Synuclein , causing micro-tubule collapse (amyloid formation) and cascades of dopamine-receptor sites’ apoptosis . Huperzine-A is one of many compounds that remove or displace TAU proteins , especially malformed ones .
Discussion :
1.The mechanism is self-evident from Appendices A – F .
A double-whammy . Synuclein reacts with the TAU protein and Dopamine receptors to form plaques and cause apoptosis . This is kept in check by Huperzine-class molecules .
There should be many more .
Why not just zap Synuclein ?
Look at Appendix E . It’s structure is so simple that any block will probably affect so many other systems that it will kill the organism .
But the dosages need an evolutionary argument .
2. Evolution :
This is a Gaian argument .
Why does the system need a mechanism to prevent stupidity ? Like the club mosses , which is only one of the sources of Huperzine-type chemicals .
It is another of Gaia’s little feedback systems . See Appendix G .
Too successful non-gymnosperm systems (ie flowers , animals , humans) decrease Gaia’s reserves . This leads to less molecules like Huperzine-A in the biosphere . This leads to the too-successful species becoming stupid , making them less successful . This will then stabilize Gaia’s gymnosperm reserves .
3. Smart animals need a continual addition to concentrations of Huperzine-class molecules to remain smart . If there insufficient mosses , they become stupid or die off .
4.Did the mastodons and mammoths kill off all the large , smart magafauna by being too efficient eaters of moss ?
5. More importantly , is this happening now to humans ?
6. Angiosperms (flowering plants : double fertilization) are intimately linked to dopamine . See Appendix H . Where poppies get the genetic machinery for dopamine production .
This then ties into this whole mechanism . Too low concentrations of Hupervine-class molecules will definitely mean the collapse of double-fertilization . A catastrophe for humans .
Conversely, planting club-mosses in between rows of plants or spraying huperzine should dramatically increase crop yields .
7. Humans should enhance gymnosperm reserves , or Gaia will do it for them .
You have been warned .
8.Dosages :
Gaia does not favour longevity .
This is rather trivial restatement that fewer generations search smaller possibility spaces .
Huperzine-class molecules should be administered so that on an age basis :
HGH(t) + Huperzines(t) = HGH(21) ,
Where HGH is Human Growth Hormone and t is age in years . HGH(21)is taken as peak of human performance . See para 9 below .
There are many feedback systems , so continuous monitoring will be required .
Beats getting stupid or slow .
9.Human peak performance :
This peak is reached at the age of 26.1 years for the disciplines studied: athletics (26.0 years), swimming (21.0 years) and chess (31.4 years). 
10.This has obvious applications .
The peak-performance plateau can be extended by proper dosages of Huperzine-class molecules . But there will be synergistic reactions .Monitoring is vital .
HGH secretagogues must be taken into account as well .
11.Will this class as doping ?
Remember , this will actually work in extending top-performance . It is not an enhancement .
Will a chess player taking these supplements be cheating ? Or any athlete ?
12. Natural persons doing it :
Not a freak . She just liked smelling the flowers .
She became famous as the first woman to run across the United States, from Los Angeles to New York City. Her route, run in 1978 as a 53-year-old grandmother, took her 2871 miles and 69 days, 2hours and 40 minutes. This record was not broken until 1993, when Lorna Michael (age 34) crossed the continent in 64 days as part of the Trans-America Footrace in 1993. [4]
13. Sociological implications :
This is not theoretical . I can go out and buy the requisite Huperzine-A tomorrow . My performance will at least plateau . With some tweaking at my age it will probably increase .
All the no 2’s waiting for the Boss to go will wait , and wait , and wait . And so down the line .
Longevity Obsolescence .
Dominant figures will remain dominant for a long time . (See why Gaia doesn’t like longevity ?)
14. Retirement Lottery .
This used to be old age or death .
If you get tired of it all , but don’t want to surrender , enter the Retirement Lottery .
If your number comes up , all titles and posts must be relinquished . Two thirds of your wealth must be given to the charity of your choice . You have to open new Facebook , Twitter , Blog and all other social media accounts . Start afresh , but with some reserves .
This sounds like more of the same . But look at what happened with the break-up of Standard Oil in the early 20th century . A nominal thing became real as ego’s clashed .
Note that many people (Gates , etc) are doing exactly that .
That is if Gaia doesn’t kill you all first .
Isn’t Ecology exciting ?
Andre .
Appendix A
“We translated our findings into a novel therapeutic approach by using a small peptide that mimics the effects of removing TAU from the synapse, and we were thrilled to see that this not only fully prevented the pathology in our Alzheimer’s disease models but cleared their memory deficits,” Dr Ittner said.
“Although there is still a long way to go we believe we may have found a way of treating Alzheimer’s disease,” adds Professor Götz.
Appendix B
Because dopamine D₂ receptors are known to be elevated in schizophrenic brain striata, this study of postmortem striata examined whether a similar dopamine receptor elevation occurred in other diseases, including neuroleptic-treated Alzheimer's, and Huntington's and Parkinson's disease patients. Findings show that compared with the neuroleptic-induced and unimodal elevations in D₂ of 31% in Alzheimer's disease and 37% in Huntington's disease, the schizophrenic striata with a mode of 26 pmol/g (105% above control) appeared to contain more D₂ receptors than could be accounted for by the neuroleptic administration alone. Parkinson's disease increased D₂ elevations in Ss not receiving levodopa. (PsycINFO Database Record (c) 2013 APA, all rights reserved)
Appendix C
Related in effects to Alzheimer’s , Parkinson’s .

Appendix D
Huperzine A is also an acetylcholinesterase inhibitor, which has a mechanism of action similar to donepezil, rivastigmine, and galantamine. A pro-drug form of huperzine A (ZT-1) is under development as a treatment for Alzheimer's disease.[3]
In the US, huperzine A is sold as a dietary supplement for memory support. The botanical has been used in China for centuries for the treatment of swelling, fever and blood disorders. Clinical trials in China have shown it to be effective in improving cognitive performance in patients with Alzheimer's disease[4] and enhancing memory in students.[5]

Appendix E
Compare the structures of TAU and Huperzine-a . Notice how Huperzine-A wraps around TAU . Hupervine-A will both inactivate and displace TAU , depending on concentrations .
See appendix A above
Synuclein wraps the loose ends of TAU . Leading to ameloid plaques .
Huperzine-A disrupts this process to a 2/3 degree . Some ends are still sticking out .

Appendix F
Notice how Synuclein in Appendix E above binds to and deactivates D2 . D2 then gets apoptosed.

Appendix G
Gaia Strikes Back !
Andre Willers
14 Nov 2010

Synopsis :
The success-rate of angiosperm reproduction has fallen due to reduction in Gaiean non-angiosperm reserves . This has major consequences for human food supplies .
(Indeed , alarm bells should be ringing loudly.)

Discussion :
See :
NewScientist 11 Sept 2010 p6 "Pollen crisis" : "The Flower , the Dinosaur and Puff" , "Tunneling Nanotubes ." and "Death of the Dinosaurs"
The effects of the decrease in Gaiean non-angiosperm reserves (mainly gymnosperms and fungi) was discussed at length . The decrease in pollinator numbers (ie bees and dependant species like frogs) was expected .

However , a new effect has appeared from 1999 onward .
(See "Philosophical Transactions of the Royal Society B , vol 365 ,p3187)
Naturally pollinated plants fared consistently worse compared to artificially pollinated plants (the effects of insect scarcity was eliminated : there was no pollinator scarcity in the test system .)

There are three possible explanations

1.Plants are producing less pollen .
2.Angiosperm double-fertilization has been reduced .
3.A combination of both .

The second possibility is truly worrisome .

The mechanism :
Some factors produced by gymnosperms and/or fungi were in balance with the angiosperm double-fertilization trick . The balance was at the discussed 1/3 non-angiosperm , 2/3 angiosperm level . This was the level about 90 million years ago .

(Typical evolutionary would be : inhibitors (A) of angiosperm double-fertilization would be inhibited by gymnosperm inhibitors(B1) and fungi inhibitors(B2) .
The success of angiosperms would then occur if B1<>B2 .
Angiosperms sort-of wriggled their way into exploiting the inequalities between the two systems .)

As the gymnosperm forests shrink (eg human deforestation , global warming) and fungal mass shrink (eg draining of marshlands , sequestering of sulfur-bearing biomass) , double-fertilization becomes rarer . B1 and B2 both shrink , leading to increased inhibition A .

The effects should be more pronounced at the borders of the three biomes .

Quorum mechanisms .
These most likely have been established , as this process has been around for about 130 million years .

This means that a sudden , catastrophic reduction of angiosperm reproduction to gymnosperm reproduction is not only possible , but likely .
Crop yields would fall by factors of 100 – 10 000 within a season .
(Something like a natural version of Monsanto's Terminator gene)

The resultant die-off of over-successful dependant species would re-establish business-as-usual from Gaia's viewpoint .

Artificial pollination in agricultural enclaves (like agricultural towers) is possible if they survive the warfare . (Cf ants and termites , who seem to have been here before)

Or else , the genetic- and bio-engineers could get off their duff .

It is doubtful if any political solution except war is possible . (Tragedy of the Commons argument)

We could awaken Gaia .
The Sleeping Princess with a vengeance .
It is definitely possible (probability about 80% in 2010)
This might happen in any case given present technology . Humans would be part of the gestalt .
(As discussed in : "Death of the Dinosaurs" )

This might seem like a political solution , but is it really ?
Does a weed negotiate with the gardener ? Only if it is smart weed and can be useful .
But autonomy would be limited .
(On the other hand , I have had spirited negotiations with crabgrass , and usually came out on the losing end.)

Interesting times in the gardens of Sol .



Appendix H
Dopamine biosynthesis at different stages of plant development in Papaver somniferum.
Latex and cell-free extracts of various organs and stages of plant and capsule development in Papaver somniferum, the opium poppy, synthesized dopamine, an alkaloid precursor, from 14C-dopa. The 1000 g X 30 min supernatant from latex of the pedicel-capsule junction converted more dopa than latex supernatant from the upper capsule or lower pedicel regions, although there was more protein in the latex from the capsule. Percent conversion of pedicel-capsule latex into dopamine was maximum in unopened flower buds and decreased within 14 days after flowering. Dopamine biosynthesis in latex and cell-free extracts also varied with the stage of organ development. Extracts from capsule tissue converted more labeled dopa into dopamine than did extracts from pedicels, leaves from vegetative plants at the rosette stage, leaves from flowering plants, or pedicels connected to capsules.

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