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Cellular metabolism – new controls are being found …There was a point in time when it was thought that most DNA was simply “junk” that serves no purpose. In fact, it was thought that more than 98% of DNA was junk DNA or non-coding DNA. Non coding DNA is DNA that they thought had no biological function. It didn’t transcribe to a protein and therefore, they thought it didn't do anything. Perhaps they thought it was simply left over. For example, as animals evolved new functions, new variations and mutations occurred. Those mutations might add something new or remove something. They also might turn something off - such as part of a strand of DNA. Thus, it could become junk DNA. But among what was thought to be junk DNA is DNA that served various other functions beyond the typical use of coding for some bit of protein. Some of the junk DNA has an impact on DNA is used and when. It is regulatory DNA. Over time, the amount of DNA that was thought to be junk declined to 90%. Now, many biologists believe that the amount of junk DNA may be closer to 20% based on “biological activity” tests. The problem is that no one as of yet understands what the purpose of much of the non-coding DNA. But just because no one has figured out what it does, does not mean it is not doing something. Within the cell, there are two main types of ribosomes. There is the one that is generally attached to the endoplasmic reticulum. And there are ribosomes within the Mitochondria. The ribosomes in the Mitochondria are different and more closely related to those of single celled organisms than to ribosomes located on animal endoplasmic reticulum. The ribosomes on the endoplasmic reticulum are more complex. Some may think this means the mitochondria ribosome is more “primitive” due to it being closer related to single cell organisms. But this is incorrect. The more complex ribosome on the endoplasmic reticulum would be needlessly complex for what is needed in the mitochondria. The ribosome that exists in the mitochondria is able to construct the proteins that are needed by the mitochondria. If it had a more complex mitochondria, it would be more flexible in the ability to construct other proteins. But given other proteins are not needed by the mitochondria. More complexity can lead to higher probability of a flaw. Single celled organisms evolved along various paths. One path was to evolve cell membranes. That path allowed the inclusion of other organelles such as mitochondria. Mitochondria were probably a type of single cell organism before being included into another single celled organism.The mitochondria may have been at first a type of parasite that evolved over time into a symbiotic relationship. Cell types with mitochondria had an advantage as mitochondria are very efficient generators of energy. Over several hundred million years, mitochondria became intrinsic to certain types of cells. That is only one of several organelle's that may have originally been part of a different single cell organism. Some of the cells that contained complex organelles evolved into multi-celled organisms such as animals. As multi-celled organisms became more complex, cells must develop ways of communicating with each other. For example, how does a skin cell know it is a skin cell? How does it notify the rest of the organism that skin cells in the area are under attack and need help from specialized immune cells? Another example, a skin cell needs few mitochondria. Yet a muscle cell or a nerve cell needs many especially muscle cells in organs like the heart. There needed to be a robust way for the cell to communicate with other cells the basic needs. For example, I’m under attack, I need more fuel, I am injured, I’m infected, I have cancer and etc. Within a cell, it must also be able to communicate with various organelles. Given each human cell has the same DNA but some cells may be brain cells and others may be in the hair follicle manufacturing the hair on the back of the hand or the back of the head. Depending on the location, the hair is even different so there are even slight variations in manufacturing of hair. Thus, within the cell, there must be robust methods of signaling a cell to develop for a specific purpose whatever it is. Within the cell, robust mechanisms that are necessary to to coordinate cellular activity and to communicate between the organelles. The cell itself must be able to change structure, or respond individually to various type of stimuli and stress. Consider a neuron. Some neurons in the brain change their structure slightly if a memory is formed. New dendrites and axons develop based on the functions that the brain is put to. I.e, if someone learns to play the guitar, their brain will change structure slightly. New dendrites and axons develop. Synapsis change. More energy is expended n different neurons, and the neurons grow and move more mitochondria and other materials to provide the needed energy and fuel the new building spree. Consider the varying messages that need to be sent within the cell and to neighboring neurons to accomplish this! Sometimes, as people age, neurons start to malfunction such that various illnesses occur. One of the major ones is Alzheimer’s disease and another is Parkinson’s disease. There has been a large amount of research into these type of illnesses and yet, it is not known exactly what causes it. However, as research is done on these and other diseases, new “cellular” controls have been found. Certain chemicals have been found to cause neurons to respond in certain ways. Some of these chemicals were discovered by accident. Those found by accident were researched to try to determine how it actually works. Researchers eventually uncovered some of the mysteries of cellular signaling that allowed researchers to develop other chemicals that may work better at manipulating cellular controls in a way that is helpful. One such chemical is Anavex 2-73 or A2-73. It is believed that this chemical in effect flips a biological "switch" or trigger that in effect tell the cell to restore "homeostasis". This does several things such as improve mitochondria to endoplasmic reticulum communication, reduce protein mis-folding, prevent tau protein buildup, and etc. By doing this, it improves cellular energy metabolism, de-stresses the neuron, prevents some series of events that often lead to cellular death. The early results from lab testing of rats and mice support the contention. The Phase 2a/b testing also supports this contention that it does flip an effective switch that helps with Alzheimer’s disease. For Anavex Life Sciences, if they have found a fundamental way to in effect use a drug to “flip a switch” in the cells that improves the health of the neuron sufficiently to prevent diseases like Alzheimer’s disease and Parkinson’s disease, it will cause a fundamental shift in people’s perceptions of those diseases. It will also save hundreds of billions of dollars to care for Alzheimer’s and Parkinson’s patients. Of course, the problem with flipping switches in the cell is that it brings up the idea of what else this switch could do? Does it have other detrimental effects over time? The list of worries is long including the worry that we are fooling ourselves that it works at all. The starting size of the 2a/b trial was after all only 32 patients. This worry is somewhat mitigated by lab results which appear to show that A2-73 has a robust biological effect. Secondly, it is mitigated by some of the curious things that it also appears to have done. For example, in the Alzheimer’s patient population, insomnia is common. In fact, sleep changes are often a large problem for Alzheimer’s patients and their care givers. Interestingly, according to the phase 2a/b results, insomnia is “cured” in the patient population. I know of people with insomnia who have tried various drugs to no avail. The question to ask would be is that some kind of placebo effect? I think it is questionable because I doubt that patients were told that the drug had anything to do with insomnia. The other thing that should not be impacted by a placebo effect is the EEG/ERP testing especially over a period of a year. The issue with doubt is that many have tried drugs to help Alzheimer’s patients. All have failed to have any lasting effect. Therefore, until there is more proof, the worry can’t be entirely laid to rest. |
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