Large Amounts of Glutamine as the Cause of Disease

Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are caused by the accumulation of abnormal proteins in neurons. An important element of cellular function is correct assimilation of proteins in cells. The protein folds into a specific structure and fulfills cell functions. However, when this folding process is performed, abnormal proteins are introduced into the cells. In neurodegenerative diseases, these protein aggregates are characterized by having genes containing multiple CAG trinucleotide repeats encoding polyglutamine (polyQ).

The interaction between the altered huntingtin protein and many proteins in neurons results in an increase in susceptibility to many of the glutamins found to be excitatory toxins. Excitatory toxins can damage many cellular structures. The content of glutamine is not so much, but it is speculated that even with the usual amount of glutamine, vulnerability increases, so excitatory toxin may develop. Although HD affects the whole brain, some areas are more vulnerable than others. The most important initial effect is a part of the basal ganglia called the new striatum, which is composed of caudate nucleus and putamen. Other affected areas include the substantia nigra, layers 3, 5 and 6 of the cerebral cortex, the hippocampus, the Purkinje cells of the cerebellum, the lateral ducts of the hypothalamus and parts of the thalamus.

What is special about glutamine? One important observation is that mTOR complex 1, mTORC1, is the major regulator of protein production and responds to glutamine levels. Growth factor signaling occurs in the presence of sufficient amino acids via the insulin-like growth factor (IGF) -PI3K - Akt pathway. I am watching this in cancer gene research. Most of them control enzymes called tyrosine kinases. A common feature of tyrosine kinase signaling associated with cell proliferation is the regulation of glucose metabolism. This does not occur in normal cells that do not proliferate. A common MYC oncogene is particularly sensitive to glutamine withdrawal