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Bit of an idea for possible CURE. Has some weight to it.


Fawkinchit

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Today i return to an older thought:

Notch Signaling

-The question is: do we increase it or decrease it?

-DAPT shows signs of helping Alzheimer's. It inhibits notch signaling. It has been said to reduce b-amyloid. The role of b-amyloid plaque with Alzheimer's has been seen but is also debated.

-Statin Drugs such as Simvastatin increases notch signaling. And has been shown to benefit stroke victims [probably with aiding neurogenesis].

This brings up the Subventricular Zone (SVZ). This is a site for neurogenesis (that is not totally based in the hippocampus). This, I believe, is playing a role

in many patient's recoveries. Statins may aid these regions. It has also been proposed that Cerebrospinal Fluid (CF) plays a role in helping nerve growth at the SVZ area [higher CF, more nerve growth].

Also involved are the roles of astrocytes and neurospheres and mir-124 microRNA and choroid plexus.

Perhaps some form of selective notch action could be an interesting route.

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Ok for the meantime I think we need to start looking for traces of potential cns damage cause by the over activation of 5ht receptors.

http://en.m.wikipedia.org/wiki/Excitotoxicity#section_2

If you take for example the overstimulation of ampk receptors by excessive glutamate we can see the damages effects by excessive release of calcium ions cause neuronal apoptosis. So, what happens with over excitation of 5ht receptors and what damage is cause?

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Studies are underway to determine whether astroglia (astrocytes <aids in neuron repair and neurogenesis>) play an instrumental role in depression, based on the link between diabetes and depression. Altered CNS glucose metabolism is seen in both these conditions, and the astroglial cells are the only cells with insulin receptors in the brain. ------Essentially, no neurotransmitter is produced without glucose. Glucose starts at the Kreb's Cycle and we end up with all those great chemicals in our brains/body. Ecstasy abuse causes long-lasting effects on glucose metabolism in the human brain. [http://www.ncbi.nlm....ubmed/11473208]

This may also be true with drugs such as LSD.

LSD has been known to increase blood flow to the brain, but also it starves the brain/body of glucose. [http://www.beckleyfo...Basel_Talk.pdf]

Somehow, there becomes a dysfunction with glucose being metabolized, and than can effect various things such as monoamine synthesis, nerve repair, neurotransmitter regulation, toxin disposal, etc;

and therein may lie the problem that some of us are facing.

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P2Y 1 and PAR-1 receptor agonists for exciting Astrocytes. ["]http://www.jneurosci...8/26/6659.full]

~Also i was interested in P2Y14 agonists.

And Par-1 agonism seems to increase platelet response density [platelet concentration at sites]. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246054/]

Platelets produce growth factors including insulin-like growth factors.

And ironically, they are the first stage of wound healing.

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A fundamental problem for biological systems is to obtain nitrogen in an easily usable form. This problem is solved by certain microorganisms capable of reducing the inert N≡N molecule (nitrogen gas) to two molecules of ammonia in one of the most remarkable reactions in biochemistry. Ammonia is the source of nitrogen for all the amino acids. The carbon backbones come from the glycolytic pathway, the pentose phosphate pathway, or the citric acid cycle.

In amino acid production, one encounters an important problem in biosynthesis, namely stereochemical control. Because all amino acids except glycine are chiral, biosynthetic pathways must generate the correct isomer with high fidelity. In each of the 19 pathways for the generation of chiral amino acids, the stereochemistry at the α-carbon atom is established by a transamination reaction that involves pyridoxal phosphate. Almost all the transaminases that catalyze these reactions descend from a common ancestor, illustrating once again that effective solutions to biochemical problems are retained throughout evolution.

Biosynthetic pathways are often highly regulated such that building-blocks are synthesized only when supplies are low. Very often, a high concentration of the final product of a pathway inhibits the activity of enzymes that function early in the pathway. Often present are allosteric enzymes capable of sensing and responding to concentrations of regulatory species. These enzymes are similar in functional properties to aspartate transcarbamoylase and its regulators. Feedback and allosteric mechanisms ensure that all twenty amino acids are maintained in sufficient amounts for protein synthesis and other processes.

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Attaching genetic messages to relatively inert adenoviruses and "infecting" patients with it, you can either silence or awaken genetic expression through either new epigenetic methods or with the cell's iRNA.

If we attach a genetic message (that mirrors the genetic message of the genetic expression we want silenced) to these adenoviruses, iRNA will recognize the virus as something that may put the cell at risk and associate that genetic message with that risk. And in doing so, will destroy or silence that genetic message/expression.

This is where the new frontier will be in this sort of model IMO.


  • This is a direct internet link i found that explains that a genetic disease that has affected children with blindness has been restored in a good deal of people (to better sight) with gene therapy. This was gene therapy that was actually done (not totally sure) but with those adenoviruses with genetic messages attached:

http://www.scientifi...erapy-blindness

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This is a great paper (read this first or skip to the DHA material and read that first):

http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=19;epage=19;aulast=Blaylock

Cold-water oceanic fish oils are rich in DHA. Most of the DHA in fish and multi-cellular organisms with access to cold-water oceanic foods originates from photosynthetic and heterotrophic microalgae, and becomes increasingly concentrated in organisms the further they are up the food chain. DHA is also commercially manufactured from microalgae; Crypthecodinium cohnii and another of the genusSchizochytrium.[4] DHA manufactured using microalgae is vegetarian.[4] Some animals with access to seafood make very little DHA through metabolism, but obtain it in the diet. However, in strict herbivores, and carnivores that do not eat seafood, DHA is manufactured internally from α-linolenic acid, a shorter omega-3 fatty acid manufactured by plants (and also occurring in animal products as obtained from plants). Eicosapentaenoic and docosapentaenoic acids are the principal products of α-linolenic acid metabolism in young men[5] and illustrates the importance of DHA production for the developing fetus and healthy breast milk.[6] Giltay, Gooren, Toorians, and Katan (2004) found rates of conversion 15% higher for women, and that those taking oral contraceptives demonstrated 10% higher DHA levels.[7]Administration of testosterone or the aromatase inhibitor anastrozole, which blocks conversion of testosterone to estradiol, reduces DHA conversion.[7] DHA is a major fatty acid in sperm and brain phospholipids and in the retina. Dietary DHA may reduce the risk of heart disease by reducing the level of blood triglycerides in humans.[8] Below-normal levels of DHA have been associated with Alzheimer's disease. A low level of DHA is also spotted in patients with retinitis pigmentosa .

Retinitis pigmentosa (RP) is a degenerative eye disease that causes severe vision impairment and blindness.[1] Sufferers will experience one or more of the following symptoms:

  • Night blindness or nyctalopia;
  • Tunnel vision (no peripheral vision);
  • Peripheral vision (no central vision);
  • Latticework vision;
  • Aversion to glare;
  • Slow adjustment from dark to light environments and vice versa;
  • Blurring of vision;
  • Poor color separation; and
  • Extreme tiredness.

-------------------------------

Alzheimer's Symptoms

---------------------------------------------

*Note the information in the paper that talks about flavinoids; flavinoids are pigments, and certain tastes are derived from them. And bioflavinoids are directly related to ketones and the citric acid cycle.

This is related to stuff i have talked about.

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Excitotoxicity, (De)polarization, Equilibrium Potentials, Ion Channels (conductance, resistance, etc)

[i've talk about this before]

Another good article: http://jpet.aspetjou.../322/2/443.full

We definitely don't want this to be due to excitotoxicity because if that is what caused it then we're dealing with permanent loss of vital neurons in the visual cortex and this is in all likeliness a permanent state for most of us. These are things that we already know though...so?

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Zyprexa reverses PCP-induced spine synapse loss

http://www.ncbi.nlm....les/PMC3158322/

Dopamine and MDMA-use

http://www.ncbi.nlm....les/PMC3037848/

Default Networks and Resting-State Networks (RSN)

http://en.wikipedia....Default_network

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462752/

*I've been looking into drugs that will help re-activate the Cingulate Cortex/Gyrus [anterior, posterior,etc] and metabolic glucose rates in those areas.

....And also Hypoxia as it relates to mental problems and HPPD.

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