A Master Regulator of the Heat Shock Response

The heat shock response is an important process in cell maintenance, a coordinated set of mechanisms that recycle damaged proteins, activated by conditions likely to cause that damage. It is not only triggered by heat, but also by a variety of other potentially damaging circumstances such as raised levels of reactive oxygen species released by mitochondria during exercise, the presence of many types of toxic molecules, and so on. Increased heat shock response is involved in some of the methods demonstrated to slow aging in laboratory animals, and a few research teams are working towards ways to trigger it safely as a therapy - though as for the prospect of artificially inducing autophagy, another of the principal cell maintenance processes, there seems to be a lot of early stage research and little concrete progress towards this goal as yet.

Heat shock proteins protect the molecules in all human and animal cells with factors that regulate their production and work as thermostats. In new research [scientists] report for the first time that a protein called translation elongation factor eEF1A1 orchestrates the entire process of the heat shock response. By doing so, eEF1A1 supports overall protein homeostasis inside the cell, ensuring that it functions properly under various internal and external stress conditions. The researchers suggest that this finding could reveal a promising, new drug target for neurodegenerative diseases and cancer.

Heat shock proteins (HSPs) chaperone other proteins, helping them to fold properly and supporting their function. With neurodegenerative diseases, neurons lack enough protective HSPs that insulate them from protein-damaging stress. A hallmark of most neurodegenerative diseases is protein misfolding. If the heat shock response could be restored to its full capacity in aging neurons, then misfolded proteins might fold properly, potentially avoiding or halting progression of diseases such as Alzheimer's, Parkinson's, or amyotrophic lateral sclerosis (ALS). In contrast, many types of cancer cells rely on HSPs to survive. Because high levels of HSPs enable cancer cells to grow and proliferate, depleting these cells of HSPs could sensitize tumors to chemotherapy and radiation therapies. "It's a bit early, but we think that eventually we could design small-molecule activators and inhibitors that tweak the heat shock response. eEF1A1 controls every single step of the heat shock response simultaneously."

The eEF1A protein is expressed in two similar forms, 1 and 2, in different tissues. Motor neurons express form 2 (eEF1A2), which does not support the heat shock response. [Researchers] believe that this is the reason why these specialized cells cannot mount the heat shock response and therefore are particularly vulnerable to stress and diseases such as ALS. The challenge in drug development will be restoring the heat shock response in motor neurons by modulating the activity of eEF1A.

Link: http://www.eurekalert.org/pub_releases/2014-09/nlmc-sit091514.php

Comments

I've often thought that many kinds of mild stress might be good for one's health - exercise, reduced calories, slight oxidative stress and maybe even things like heat, cold, mild diseases, fleeting oxygen deprivation and brief mild dehydration. Just don't over-do it.

"That which does not kill us makes us stronger." - Nietzsche

Posted by: Allen Alger at September 17th, 2014 11:13 AM

There might be an easy way to trigger heat shock protein production: sharp EMF pulses nearby.

I think the Lakhovsky device might not have been quackery after all if it triggered this sort of hormetic reaction.

Posted by: chris zell at September 17th, 2014 12:13 PM
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