Rat study in Cell Death & Differentiation shows that PHLPP affects helpful AKT protein.
University of Florida researchers have discovered why some brain cells necessary for healthy memory can survive old age or disease while similar cells nearby die. An enzyme in the hippocampus blocks the beneficial effects of a protein that hinders many naturally occurring inducers of cell death.
Using rats of varying ages, scientists focused on neighboring regions of the hippocampus. “We looked at an important signaling pathway that tells cells to stay alive or die, and the enzymes that regulate that pathway,” expxlains 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.
Their observations suggest that the enzyme PH domain leucine-rich repeat protein phosphatase (PHLPP) may be silencing vital cell-survival protein AKT where neurons are most susceptible to damage and death, according to the researchers.
The team studied the region for signs of AKT , a protein that when activated 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 next step was to figure out what was turning off AKT in the vulnerable cells, which led scientists to PHLPP1, a recently discovered enzyme that is believed to be a natural tumor suppressor. The found that in the area with the vulnerable cells, when PHLPP1 levels were high, AKT activation was far less robust.
The discovery is published online ahead of print in Cell Death & Differentiation.