Enzyme behind slow memory process in aging brains unveiled

December 11th, 2008 - 2:34 pm ICT by ANI  

Washington, December 11 (ANI): University of Florida researchers may have moved a step closer to developing effective treatments for age-related memory loss, as they have found out why some brain cells necessary for healthy memory can survive old age or disease, while similar other cells die.
Describing their work in the journal Cell Death & Differentiation, the researchers revealed that they analysed two neighbouring regions of a tiny brain structure called the hippocampus, which is known to be central to the formation of memories, in rats of varying ages.
The research team from the universitys Evelyn F. and William L. McKnight Brain Institute found that a recently discovered enzyme, known as PHLPP (pronounced “flip”), might be silencing a vital cell-survival protein in the region where neurons are most susceptible to damage and death.
“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?” said Travis C. Jackson, a graduate student working with Thomas C. Foster, Ph.D., the Evelyn F. McKnight chair for research on aging and memory at UF.
“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 researcher added.
The scientists studied both regions for signs of a protein called AKT, which actually hinders many naturally occurring inducers of cell death. They found that activated AKT was scarce among the cells that are vulnerable to damage and death and more abundant within the hardier cells.
The researchers then set out to study what was turning off AKT in the vulnerable cells, which led them to PHLPP1.
Where PHLPP1 levels were high, AKT activation was far less robust.
“Possibly, we have found a target that could be manipulated with drugs so that these brain cells can be saved from threats,” said Foster, a professor of neuroscience at the UF College of Medicine.
“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,” the researcher said.
Alexandra Newton, Ph.D., a professor of pharmacology at the University of California, San Diego, whose team discovered PHLPP in 2005, said: “Basically, PHLPP is important in controlling whether cells survive and proliferate or die.”
The scientist who did not participated in the UF research added: “If you want cells to survive brain disease, diabetes or heart disease, you want active AKT signalling 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.” (ANI)

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