Introduction: What they say
A study from Institute for Cell Biology, University of Bonn, Ulrich-Haberland Str. Bonn, Germany; and Institute for Genetics and CECAD Research Center, University of Cologne, Joseph-Stelzmann Str. Cologne, Germany shows that “The Ubiquitin Ligase CHIP Integrates Proteostasis and Aging by Regulation of Insulin Receptor Turnover.” This research paper was published, in the 20 April 2017 issue of the journal “Cell” [One of the best research journals in Biology with an I.F of 28 plus], by Prof. Hoppe T,Tawo R and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Heat shock protein inhibitors as longevity-promoters: 17-DMAG, an HSP(heat shock protein)-90 inhibitor, increases CHIP levels, increases monoubiquitylation of insulin receptor (INSR), decreases INSR protein levels and enhances lifespan, via down regulation of its target gene
What is known?
Prof. Hoppe T’s research team has recently shown that knocking down CHIP gene in mice results in a) increased protein levels of insulin receptor (INSR); and b) reduced lifespan. Further, they have shown that CHIP targets INSR for mono ubiquitylation and degradation, while its ability to degrade INSR is compromised upon proteotoxic stress and during ageing, as CHIP is directed toward disposal of misfolded proteins rather than degrade the INSR.
From Research findings to Therapeutic opportunity:
This study provides, for the first time, mechanistic insights into how 17-DMAG may function as a longevity promoter.
17-DMAG(17-Dimethylaminoethylamino-17-demethoxygeldanamycin), by decreasing the expression of its target gene, it may increase the levels of CHIP (carboxy terminus of Hsc70 interacting protein). Thereby, it may: (1) increase CHIP-assisted proteolysis; (2) increase mono ubiquitylation and degradation of INSR; (3) inhibit the insulin and IGF1 signaling pathway; and (4) enhance longevity (Fig1).
Thus, pharmacological formulations encompassing “17-DMAG or its analogues, either alone or in combination with compounds,” may be used to suppress age-associated overall physiological decline and improve health/life span.
Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/
Undisclosed mechanistic information: How 17-DMAG decreases the levels of INSR and promotes longevity
# Research cooperation
Web: http://genomediscovery.org or http://newbioideas.com
Citation: Boominathan, L., Heat shock protein inhibitors as longevity-promoters: 17-DMAG, an HSP(heat shock protein)-90 inhibitor, increases CHIP levels, increases monoubiquitylation of insulin receptor (INSR), decreases INSR protein levels and enhances lifespan via down regulation of its target gene, 12/July/2018, 12.20 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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