Amino acid-derived therapy for Inflammatory bowel disease: L-Leucine, the branched chain amino acid, promotes NFKB-p50/p65 dimer formation, induces inflammatory gene expression downstream of RelA/p65, inhibits colonic pathogenesis, and stalls the progression of inflammatory bowel disease and colitis via down regulation of its target gene, 16/May/2017, 11.59 pm

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Introduction: What they say:

A study from the Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg, University of Mainz, Obere Zahlbarer Str, Mainz, Germany shows that increased levels of Bcl-3 inhibits Treg development and function and thereby promotes spontaneous colitis. This study was published, in the 28 April 2017 issue of the journal “Nature communications”, by Prof. Nadine Hövelmeyer, Sonja Reißig and others.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Amino acidderived therapy for Inflammatory bowel disease: L-Leucine, the branched chain amino acid,  promotes NFKB-p50/p65 dimer formation, induces inflammatory gene expression downstream of RelA/p65, inhibits colonic pathogenesis, and stalls the progression of inflammatory bowel disease and colitis via down regulation of its target gene


What is known?

Prof. Nadine Hövelmeyer’s research team has recently shown that: (1) Bcl-3 is overexpressed in patients with inflammatory bowel disease (IBD); (2) T-cell specific overexpression of Bcl-3 results in spontaneous colitis, inhibition of NFKB function, decreased Foxp3, IL-10, CTLA-4, GITR and IL-2R expression; (3) increased expression of Bcl-3 inhibits Treg (regulatory T) cell development and function and expansion of γd T-cells; (4) increased expression of Bcl-3 promotes gut inflammation and severe colitis, suggesting that Bcl-3 inhibitors may be used to inhibit the progression of inflammatory bowel disease and colitis.


From Significance of the study to Public health relevance:

Given that: (1) Colitis affects 10-12 people/100, 000/annum in the US; (2) about 1 million people suffer from inflammatory bowel disease, characterized by infiltration of T-cells that damage colon, in the US, while in Europe it is 2.5 million; (3) inflammatory bowel disease is more common in westernized nations, including North america and Europe, and in industrialized countries; (4) the incidence of colitis and inflammatory bowel disease is on the rise globally, (5) molecular pathways involved and the mechanism of development of colitis and inflammatory bowel disease is far from understood; (6) substantial amount is spent each year globally for the treatment of colitis and inflammatory bowel disease, there is an urgent need to find: (i) a way to cure colitis and inflammatory bowel disease; (ii) a cheaper alternative to the existing expensive drugs; and (iii) a side-effect-free-Natural product-based drug that permanently cures, not just treats, colitis and inflammatory bowel disease.


From Research Findings to Therapeutic opportunity:

This study suggests an Amino acid-based therapy for inflammatory bowel disease and colitis. Leucine, by regulating the expression of its target genes, it may: (1) increase DNA binding of p50/p50 and p50/p65 NF-KB dimers, and thereby promote NFKB function; (2) increase the expression of inflammatory genes that function down stream of NFKB; (3) increase the expression of Foxp3, IL-10, CTLA-4, GITR and IL-2R; (4) promote Treg cell development; (5) inhibit colonic pathogenesis; (6) inhibit the progression of inflammatory bowel disease and colitis.

Figure 1. Mechanistic insights into how the branched chain amino acid L-Leucine inhibits inflammatory bowel disease and colitis.

Together, pharmacological formulations encompassingLeucine or its analogues, either alone or in combination with other drugs”, may be used to treat inflammatory bowel disease and colitis.


Details of the research findings:

Idea Proposed/Formulated by: Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Undisclosed mechanistic information: How Leucine activates p50/p65-NFKB to inhibit the progression of inflammatory bowel disease and colitis

Amount: $500

# Research cooperation


References:

Web: http://genomediscovery.org or http://newbioideas.com

Citation: Boominathan, L., Amino acidderived therapy for Inflammatory bowel disease: L-Leucine, the branched chain amino acid,  promotes NFKB-p50/p65 dimer formation, induces inflammatory gene expression downstream of RelA/p65, inhibits colonic pathogenesis, and stalls the progression of inflammatory bowel disease and colitis via down regulation of its target gene, 16/May/2017, 11.59 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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