WHY WE USE RESVERATROL 

MICRO-RNA-155 IS OVER EXPRESSED IN DS

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This article is the first in a series explaining why we utilize certain nutrients, proteins and polyphenols to down regulate genes that are over expressed in Down syndrome. We will also discuss measures taken to manipulate proteins and enzymes that may be too low or otherwise imbalanced.

What are MICRORNAS

 MicroRNAs (mRNAs) constitute a recently discovered class of non-coding RNAs that play key roles in the regulation of gene expression. Acting at the post-transcriptional level, these fascinating molecules may fine-tune the expression of as much as 30% of all mammalian protein-encoding genes.

For a complete description of these non protein encoding RNAs please see the following.

MICRORNAS

Several of these are mapped to the critical region of chromosome 21 and are over expressed in Down syndrome. The result is a myriad of associated diseases, protein disruptions, and complications including neuro inflammation, leaky blood brain barrier, auto immune diseases, skin disorders and even leukemia and some cancers. In fact, breast cancer, association with mRNA-155, is one of the very few solid tumor malignancies found in adult women with DS. They are heavily implicated in cognitive dysfunction. Therefore, it is imperative that we address this RNA by down regulation.

Down regulation can be accomplished several ways but with very few and specific substances. These substances are of a unique chemical composition and structure that they interfere with the transcription of gene products and, in this case, MicroRNAs. In order to inhibit or down regulate a gene (to bring the levels down to normal) a substance acts to halt the creation of a gene product or RNA or to inhibit the gene product at a receptor site. This method is perfected by antagonists. We will look at this when we discuss GABA and Gingko Biloba.

MicroRNA-155 is over expressed in DS, there are three active copies rather than the normal two. In order to down regulate this mRNA we must interact with the mRNA that regulates it, MicroRNA-633. The only known substance capable of doing this is the Polyphenol, Resveratrol. Resveratrol is a substance refined from grape skins or from a plant called Japanese Knotweed. Resveratrol has been studied extensively and is safe and effective not only in down regulation of this Micro-RNA but in a recent study in Spain by Rosa Anna Vacca et. al. the combination of Resveratrol and a plant catichen, EGCG derived mostly from green tea, worked in concert to improve mitochondrial function which is impaired in DS.

For these reasons, Resveratrol is a critical component in the Nutrivene protocol. The following peer reviewed, published studies will help you understand the implications of over expressed mRNA-155 and how we are able to control it.

Molecule of the month: mRNA and Down Syndrome 

MicroRNAs and intellectual disability (ID) in Down syndrome, X-linked ID, and Fragile X syndrome

miRNA-155 up-regulation and complement factor H (CFH) deficits in Down’s Syndrome.

Analysis of microRNA expression profile by small RNA sequencing in Down syndrome fetuses.

Trisomy-21 gene dosage overexpression of miRNAs results in the haploinsufficiency of specific target proteins

Integrated miRNA and mRNA expression profiling in fetal hippocampus with Down syndrome

MicroRNA-155 negatively affects blood–brain barrier function during neuroinflammation

Why inflammation leads to a leaky blood-brain barrier: MicroRNA-155

MicroRNA-155 contributes to shear-resistant leukocyte adhesion to human brain endothelium in vitro

Studies in Resveratrol

Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD

Resveratrol, MicroRNAs, Inflammation, and Cancer

Resveratrol Down Regulates MicroRNAs

The polyphenols resveratrol and epigallocatechin-3-gallate restore the severe impairment of mitochondria in hippocampal progenitor cells from a Down syndrome mouse model