Stress Reward and Unfolded Protein Response(UPR)

Failure of the folding protein response will lead to inability to fold proteins that are necessary for proper mitochondrial function and cell survival.  Calcium overload and ensuing reactive oxygen signaling will lead to apoptosis. This is characteristic of Alzheimer's, Parkinson's and Huntington's diseases.

Psychological stress, which could stem from nutritional deprivation, that results in unfolded proteins, prompts the unfolded protein stress response(UPR). In addition to folding the unfolded protein, there is the breakdown, of misfolded protein yielding amyloid peptides, and of sphingomyelin to yield ceramide. The exosomes containing amyloid peptides and ceramide are themselves problematic outside the nerve cells as they form plaque that prevents the transmission of nerve signals.

During the endoplasmic reticulum(ER) stress, serotonin is released in the brain, in response, to counter the stress--and there is craving for protein-rich food(among other reward-seeking behaviors) due to decreased protein synthesis, which again makes the ER stress worse, thus promoting aging. Serotonin leads to decreased peripheral organ metabolism and wasting, but increased sphingomyelin synthesis in the brain, which in turn activates the UPR to stem Alzheimer's, Parkinson's  and Huntington's diseases.

Moderation is the key to proper biological activation and response. Systems have to reboot after activity. Tackling a problem at the head is better than handling it at the tail-end.

Dr. Oliver Verbe Birnso, MD.

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