Preventing and reversing memory loss is a key field of research in the area of prolonging human life spans. While humans are living much longer than they once did, many suffer from debilitating conditions such as Alzheimer's disease, which limit their quality of life during their later years.
Scientists at the University of Florida may have gained a significant insight into understanding what causes some brain cells to die, triggering these diseases, while others cells remain alive. The studies, performed on mice examined two neighboring regions in the hippocampus; an anatomical region shaped something like a curved kidney bean. The region is thought to be central to the formation of memories, and is one of the first regions affected by brain blood flow problems or Alzheimer's.
What researchers discovered was that the higher susceptibility to cell death in part of the hippocampus versus the other region was due to the enzyme PHLPP, pronounced "flip", silences the transcription of a gene that produces a critical protein to cell survival, AKT. AKT inhibits many causes of cell death. The inactivation in essence, amounts to the cell flipping its own kill switch.
Thomas C. Foster, Ph.D., the Evelyn F. McKnight chair for research on aging and memory at UF describes, "The question is why does one set of brain cells live and another set die when they are only millimeters apart in the same small brain structure? We looked at an important signaling pathway that tells cells to stay alive or die, and the enzymes that regulate that pathway. Implicated in all this is a new protein that before a couple of years ago no one actually knew much about."
The conclusions were drawn by first finding AKT levels to be a key chemical difference between the living and dying cells. From there, the cause of the AKT shortage was traced to high levels of the enzyme PHLPP1, the mouse version of PHLPP, an enzyme found in other mammals. Ironically, the recently discovered enzyme suppresses tumors in many cases. The compound was discovered by Alexandra Newton, Ph.D., a professor of pharmacology at the University of California, San Diego.
Professor Newton comments on the new research, stating, "Basically, PHLPP is important in controlling whether cells survive and proliferate or die. If you want cells to survive brain disease, diabetes or heart disease, you want active AKT signaling and therefore low PHLPP. But if you want to stop cells that have the 'go' signal, like cancer cells, PHLPP can function as a brake. In this case, it appears as if there is an area in the hippocampus that is easily stressed and might undergo ischemia easily, because PHLPP is not allowing the AKT survival mechanism to work."
According to Professor Foster, the breakthrough could lead to new drugs to combat memory loss and brain damage. He states, "Possibly, we have found a target that could be manipulated with drugs so that these brain cells can be saved from threats. If one area of the hippocampus has a deficiency in cell-survival signaling, it is possible to find a way to ramp up the AKT protein. The caveat is, there are studies that show over-activating AKT may not be good for memory — AKT may be naturally lower in this region for an important reason. But in times of intense damage, there may be a therapeutic window to upregulate AKT and get some benefit to health."
It is still unknown why some regions of the brain flip the switch to trigger cell death, while others, which appear equally vulnerable to tumor formation, do not.
The research is published online in the Nature publication Cell Death & Differentiation.
quote: Brain cells are basically irreplaceable. The more you drink the dumber you get.
quote: Same goes with anything that starves your brain of oxygen or alters the chemical balance of your brain cells.
quote: Smoking pot to get high your whole life will ultimately leave you dumber than a box of rocks.