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Latest Network Analysis Results

I would like now to present the latest results as these where found using Network Analysis. The Network Analysis graph that has been presented so far was generated on April 2017. Since then many more topics were added and considered using both Network Analysis and Machine Learning Techniques.

Before continuing, please read the following Disclaimer :

The information discussed in this Blog and this Post is purely informational and does not constitute any Medical Advice of any Kind. If you are a patient do not take any chances with your Health. Talk to a Certified Health Professional.

The Network Analysis Graph (of which a specific area is shown) looks as follows :




From the Network Analysis we may hypothesise the following :

-The potentially  important roles of NAD (Nicotinamide Adenine Dinucleotide)  and Tocotrienol. The reason for which Tocotrienol is considered important requires further Research.

-The central roles of Flavoproteins and particularly FMN (Flavin Mononucleotide)

-The importance of NAFLD (Non-Alcoholic Fatty Liver Disease) and Steatohepatitis. LXR is also shown. Note also “Hydrolysis” node  between LXR and NAFLD Nodes.

-The role of Actins (F-Actin and G-Actin) both of which were discussed in previous posts.

-Note also T-Cell node in the upper far right side of the snapshot.

-Other potential targets of interest : NDUFS7 and P5P (Coenzymated B6)

We also notice a node named Glycoproteins. From Wikipedia we read :


“Glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a co-translational or posttranslational modification. This process is known as glycosylation.”

A specific class of Glycans called N-Glycans (synthesized through N-Glycosylation) deserve more attention. N-Linked Glycosylation requires a lipid called Dolichol phosphate. According to WIkipedia, Dolichol phosphate is a product of Hmg-CoA reductase pathway :

"Dolichol is a product of the HMG-CoA reductase pathway (also known as the mevalonate pathway), and as such their creation and availability are affected by mevalonate inhibition"

Coming back to N-Glycans we read from Wikipedia [2]:

"N-linked glycans are extremely important in proper protein folding in eukaryotic cells. Chaperone proteins in the endoplasmic reticulum, such as calnexin and calreticulin, bind to the three glucose residues present on the core N-linked glycan. These chaperone proteins then serve to aid in the folding of the protein that the glycan is attached to. Following proper folding, the three glucose residues are removed, and the glycan moves on to further processing reactions. If the protein fails to fold properly, the three glucose residues are reattached, allowing the protein to re-associate with the chaperones. This cycle may repeat several times until a protein reaches its proper conformation. If a protein repeatedly fails to properly fold, it is excreted from the endoplasmic reticulum and degraded by cytoplasmic proteases."

Therefore, N-Linked Glucosylation is required for the proper folding and quality control of proteins in the Endoplasmic Reticulum. In [1] we read : 

The presence of glycans on proteins is known to influence their stability and solubility and the glycan core can contribute to folding processes. N-glycans also influence the function and activity of proteins. The terminal residues of N-glycans play a key role in the quality control of protein folding in the ER. Ultimately the glycan signals whether a protein is correctly folded and can leave the ER to continue its maturation in the Golgi or whether the protein is not correctly folded and is degraded . It is therefore of great importance that the oligosaccharide to be transferred to proteins is complete. This “quality control” of the oligosaccharide is mediated by the substrate specificity of oligosaccharyltransferase.

Please note that the potential importance of ER Stress and Unfolded Protein Response has been discussed in previous posts.


Having discussed about Glycosylation and N-Glycans, in a paper named  "Glycolysis and glutaminolysis cooperatively control T cell function by limiting metabolite supply to N-glycosylation" [3] we read  the following excerpts, 

-Connection of N-Glycans with T Cells :


"In T cells, N-glycan branching regulates development, growth, differentiation and autoimmunity by altering T cell receptor clustering/signaling, surface retention/localization of CD4, CD8, CD45 and CTLA-4, and the differentiation into pro-inflammatory TH1 over anti-inflammatory TH2 cells"

In a previous post we discussed about the association of LXR with Glucokinase

"Fructose-6-phosphate is derived from glucose by the action of hexokinase/glucokinase (HK) followed by glucose-6-phosphate isomerase (GPI) and is the critical entry step into glycolysis via the key regulatory enzyme phosphofructokinase 1 (PFK1)"

Interestingly a supplement called N-Acetylglucosamine (NAG / GlcNAc) is mentioned in the same paper :


"The ability of GlcNAc to promote iTreg while blocking TH17 differentiation further validates its potential as a therapeutic for autoimmune disorders. We have previously shown that GlcNAc limits T cell activation/growth and when provided orally to mice, inhibits experimental autoimmune encephalomyelitis, a mouse model of Multiple Sclerosis (MS), as well as autoimmune diabetes in the Non Obese Diabetic mouse model (Grigorian et al., 2011, 2007). GlcNAc has also been given orally (3– 6 g/day) to children with refractory inflammatory bowel disease for ~2 years, with 8 of 12 showing clinical improvement without reported toxicities and/or side effects (Salvatore et al., 2000). We have recently observed that serum levels of endogenous GlcNAc are markedly reduced in patients with the progressive form of MS and correlate with clinical disability and imaging measures of neuro- degeneration (Alexander Brandt and Michael Demetriou, unpublished data). A pilot study of low- dose oral GlcNAc in MS (3 g/day) increased serum GlcNAc levels and branching in T cells (Barbara Newton and Michael Demetriou, unpublished data). As GlcNAc is a dietary supplement that is for sale ‘over the counter’ in the US, these data suggest that GlcNAc may serve as a safe and inexpensive therapeutic for MS patients and potentially other autoimmune diseases."



References :



[2] : https://en.wikipedia.org/wiki/Glycan

[3] : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5257256/


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