Genes, Proteins and Regulation by Nature 

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

We are getting very near the end of lessons. What remains is how certain genes damage your child and how food and their extracts work with the human genome.  This will not cover every single gene, as again, that belongs in the advanced group. It will focus on those genes and proteins that most profoundly effect the negative pathology of Down syndrome; cognition, hypotonia, heart defects, immune response and blood disorders. We will group these into genes located on C21 and proteins located or not located on C21 but adversely effected by Down syndrome and involved in its pathology. Lastly, we will look at telomeres in DS. Note, the studies will not be in the exact order as the lists. This lesson will cover APP, S100B, Inflammatory cytokines (IL1 and 2). Each lesson hereafter will follow the same pattern by identifying the gene or protein.

It is impossible to ask you to understand every single gene or substance utilized to combat it. But we will focus on the most important.

Let’s get going.

The genes we will ultimately examine are SOD1, RCAN1, SNX7, (b)APP, DYRK1a, COX2, COLV1, mRNA-155, mRNA-126b, CBS, IL1, IL2, CAN, TNFa, S100B

Proteins: MECP2, HRF/TCTP, TAU, Peroxynitrite (toxin), Superoxide (toxin), CREB, ATP, Neuro Histamine, IL10,

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In this lesson, we will look at APP, S100B and IL1 and 2.

Problems: IL1, (b)APP, S100B and cognition
NOTE: Although green tea, or a substance derived from it, EGCG has been shown to naturally effect S100B, it does so in a dose dependent manner.  EGCG will not inhibit or upregulate S100B. However, a spice, Curcumin has been shown to down regulate S100B. This demonstrates how some foods work synergistically.

“Two chromosome 21-based gene products, β-amyloid precursor protein (βAPP) and S100B, have been implicated in these neuronal and interstitial changes. Although not necessary for mental retardation and other features, βAPP gene triplication is necessary, although perhaps not sufficient, for development of Alzheimer pathology. S100B is overexpressed throughout life in Down patients, and mice with extra copies of the S100B gene have dendritic abnormalities. “

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3833615/

IL1, (b)APP, S100B and Neuro Inflammation

“The discovery of neuroinflammatory changes, including dramatic proliferation of activated glia overexpressing a chromosome 2 gene product – the pluripotent immune cytokine interleukin-1 (IL-1) – and a chromosome 21 gene product – S100B – in the brains of fetuses, neonates, and children with DS opened the possibility that early events in Alzheimer pathogenesis were driven by cytokines.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750399/

Problems: Calcineurin, S100B (low in DS) TNFa CBS and IL2

“…it can be concluded that excessive synthesis of multiple gene products derived from overexpression of the genes present on chromosome 21 may be the cause for decreased immunity in DS patients compared to controls.”

https://www.sciencedirect.com/science/article/pii/S1110863013000372

Here we see that only a very few of the genes involved are enough to result in cognitive decline and life long impaired immune response. If these were the only contributors, I would be rejoicing. Certainly as few as three drugs could be developed to combat these. But, unfortunately, these are joined and complicated by the other genes and proteins listed above and numerous others not listed. No drug targeting just one will do anything of a permanent nature to help your child. It is scientifically impossible. Combining pharmaceutical inhibitors is also a serious concern due to drug interactions and side effects. But nature (G-d) has designed the human genome to work with foods. These foods contain proteins, Polyphenols, vitamins, minerals, oils, catechins, antioxidants, etc. that directly interact to keep the genome.

For instance, EGCG found highest in green tea interacts with several of the genes and proteins listed above. If you choose to use green tea, always adhere to FDA guidelines concerning safety.  Let’s look at some studies. Since we are discussing EGCGs effect on genes and proteins, it is not necessary that the studies focus on Alzheimer’s disease or Down syndrome. However EGCG has been studied successfully in both mouse models and human Trisomy 21 patients.

https://pubs.acs.org/doi/abs/10.1021/am501341u?src=recsys&journalCode=aamick

http://irjns.org/article-1-87-en.pdf

https://www.ncbi.nlm.nih.gov/pubmed/29292676

https://www.ncbi.nlm.nih.gov/pubmed/16177050

(As a DYRK1A inhibitor- this will be repeated in the next study-https://www.ncbi.nlm.nih.gov/pubmed/24039182)

Let’s move on to inflammation and immune modulators, Interleukins 1 and 2.

Curcumin, actually a spice, directly inhibits or modulates several genes that are over expressed in DS. The interesting thing is that Curcumin and EGCG overlap. Curcumin targets inflammation and in particular, Interleukins 1 and 2 greatly inhibiting the neuro inflammation and poor immune response related to these two over expressed ILs.

IL1
https://www.ncbi.nlm.nih.gov/pubmed/16046709

IL2
https://www.ncbi.nlm.nih.gov/pubmed/29127008

Curcumin and amyloid plaque (APP)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2781139/

http://www.jbc.org/content/280/7/5892.short

Curcumin and existing amyloid plaque (APP)

https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1471-4159.2007.04613.x

At present, no food has been identified that has a regulating effect on the CBS gene.

Studies on drugs designed to inhibit a very few genes have largely been ineffective. Why? The answer is really very simple, DS is too complex to benefit extensively from the down regulation of just one gene.

THE FDA PROHIBITS EVEN INDIVIDUALS FROM MAKING MEDICAL CLAIMS FOR NUTRITIONAL SUPPLEMENTS. THE FOLLOWING 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.