Most
citations used are taken from the NLM database and are in the public domain.

LESSON FOUR Understanding How Food Substances Effect Gene Regulation

There are three ways foods or food substances  may prevent a protein from doing harm, the first is inhibition. Inhibition occurs usually at translation though it may be possible to do so at transcription. Within the nucleus of the cell, genes copy the “recipe” for a protein to mRNA (messenger RNA)
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https://en.m.wikipedia.org/wiki/Messenger_RNA.
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mRNA leaves the nucleus through pores in the two coverings housing the nucleus.
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https://en.m.wikibooks.org/wiki/Cell_Biology/Organelles/Nucleus
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mRNA conveys the recipe to the factory, a Ribosome.
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https://en.m.wikipedia.org/wiki/Ribosome
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Ribosome is a technical term for an actual machine which can both read the recipe and collect the ingredients to create the gene product.
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Think of this as a factory with a conveyor belt. When inhibition occurs at translation (where the ribosome reads the recipe) it is the equivalent of a lever being inserted into a mechanism to stop the conveyor from moving the recipe to the place in the factory where it is read (translated). Only certain things with specific chemical structures can fit as a lever into the mechanism. Similar to how an enzyme is actually shaped to fit into an identical inverse shape in a substrate. Like a puzzle piece. Let’s look at the DYRK1a gene which is over expressed in DS. This tyrosine/serine dual kinase is inhibited at translation. EGCG, a substance found in green tea, has the correct chemical structure to become the lever to stop the conveyor belt. But it’s more exciting than that. When EGCG enters the cell it actually targets those proteins that it enteracts with.  This lowers the levels of DYRK1a in each cell. Remember, we do not want to inhibit ALL DYRK1a, only reduce it to the level that would be in each cell if the kids had only two DYRK1a genes.

PLEASE READ

DYRK1a- How it’s over expression effects Down syndrome

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111700/
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https://www.ncbi.nlm.nih.gov/pubmed/2703075
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https://www.nature.com/articles/s41598-017-00682-y
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How Inhibition rescues cognition

https://www.nature.com/articles/s41598-018-20984-z
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How EGCG Inhibits DYRK1a

EGCG inhibits DYRK1A

EGCG Rescues Cognition in both mice and human beings

https://www.ncbi.nlm.nih.gov/pubmed/24039182
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In very high doses EGCG may harm the liver. DO NOT FDA exceed recommended dosages.

EGCG Protects the liver

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536772/

A second method, antagonists, does not lower the levels of excess proteins. This method blocks the protein at the receptor. Think of this as a door to the cell that has been closed.
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https://en.m.wikipedia.org/wiki/Receptor_antagonist
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Though I do not use it, Ginkgo Biloba is a GABA receptor antagonist. Let’s look at neurons. Each neuron has a receptor cite that receives the influx of the neurotransmitter. It is specific to the chemical structure of each neurotransmitter.
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Ginkgo Biloba rushes to the receptor cite blocking it and preventing the neuron from receiving the chemical neurotransmitter, GABA. NOTE not all kids with DS have a need for GABA inhibition. If your child is very slow and laid back you may want to use Ginkgo Biloba. The issue with Ginkgo is that our children are prone to seizures and on rare occasion, Ginkgo has been known to trigger them. In a recent study of a pharmaceutical GABA antagonist, it was found to provide no benefit at all in children with Down syndrome. It is reasonable to say that there may be an imbalance of neuro transmitters in the brain.

Valerian is not a GABA antagonist, but acts within the GABA pathway while binding to the receptor. This effect seems to balance neurotransmitters.  Not every child needs a GABA antagonist.

Third, there are certain proteins that compete with other proteins. Let’s look at tryptophan which is low in DS. It is the precursor for the neurotransmitter Serotonin. In DS, a small percent of children do produce sufficient serotonin which may be due to diets rich in tryptophan. Let’s pretend that Serotonin is high in DS for the purpose of this discussion. We would control this via the third method “competition”. Several amino acids actually compete with tryptophan, similar to one person pushing someone aside and running ahead of them to win a race. One would choose the right amino acid in competition and ingest greater levels of foods containing this amino acid while, at the same time, reducing the consumption of foods containing tryptophan and introducing foods containing our chosen amino acid. The competitors for tryptophan are isoleucine, leucine, phenylalanine , tyrosine and valine. This method is “competition.
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In DS there are also proteins that are too low. Certain foods or food substances encourage a gene to over produce. This can be done by precursors (those proteins required for the creation of the substance) or by those things that encourage a gene to make more of the protein. Let’s look at Glutathione. Glutathione is very low in DS due to the over expression of the CBS gene. The best form of Glutathione is called reduced Glutathione which is actually the three amino acids it is constructed of, except we use a specialized product called Setria. This method of reducing the size of the Glutathione molecule permits it to cross the blood brain barrier, but we also introduce selenium. Selenium encourages the gene to produce more Glutathione. But, because too much selenium is toxic, you must be very careful.  As your child reaches adulthood, his or her homocysteine levels may rise. Your doctor should add homocysteine to his regular blood work panel and monitor it regularly. When homocysteine is high, n-acetylene cysteine or NAC. NAC has been proven to help maintain stores of Glutathione and to lower homocysteine.

Information on Valerian Root

Valerien root and Insomnia
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http://www.sleep-journal.com/article/S1389-9457(10)00100-0/references

Important Valerian reduced elevated SOD1

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506936/

https://www.ncbi.nlm.nih.gov/pubmed/19375459

Improves learning and memory increasing cholinergic activity in the brain

https://www.ncbi.nlm.nih.gov/pubmed/16579738

Helps regulate GABA

https://www.ncbi.nlm.nih.gov/pubmed/14742369

Is Effective for Hyperactivity, OCD

http://www.sciencedirect.com/science/article/pii/S0944711314001494?via%3Dihub

Mediates Cortical excitatory circuits which makes it beneficial for preventing seizures

https://www.ncbi.nlm.nih.gov/pubmed/29035887

Nervous agitation in children can be greatly reduced

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580146/

Sleep disorders in children. Obstructive sleep apnea is common children with DS and must be ruled out. During the night, children with OSA May suffer periods where they do not breathe and oxygen levels drop alarmingly. This can result in hypoxia. Hypoxia causes inflammation and, if the levels drop low enough for long enough, your child could suffer brain damage.

Read the following

Obstructive Sleep Apnea in DS

https://www.ncbi.nlm.nih.gov/pubmed/28544488

https://www.ncbi.nlm.nih.gov/pubmed/12120807

Valerian protects against neurotoxicity in neurons

http://www.mdpi.com/1420-3049/17/12/15013

And down regulates the expression COX2

https://www.ncbi.nlm.nih.gov/pubmed/20845789u

THE FDA PROHIBITS EVEN INDIVIDUALS FROM MAKING MEDICAL CLAIMS FOR NUTRITIONAL SUPPLEMENTS. MENTION OF NUTRIONAL SUPPLEMENTS IS PROVIDED BASED ONLY ON THE ATTACHED RESEARCH TO EXPLAIN HOW THE HUMAN GENOME RESPONDS TO FOOD SUBSTANCES AND IS NOT INTENDED AS MEDICAL OR CURATIVE ADVICE.