Researchers found a clue to how degenerative brain disease develops with help from an unlikely source–yeast. Yeast interacts with other genes in a way that has remained unchanged over evolutionary time and is similar to the way plant and animal genes interact.
What researchers found was a link between a virtually unknown signaling molecule and neuron health. The molecule is PI(3,5)P2 and is a lipid that is found in all cells at very low levels. Lipids are fats, waxes, and oils and PI(3,5)P2 is in an unique class of lipids that signal the cell to perform special tasks. For the researchers, it was surprising that PI(3,5)P2 plays a significant role in the survival of nervous system cells.
Mice that had low levels of PI(3,5)P2 had profound neurodegeneration, which suggests that it is a good area to investigate for treatments for diseases like Alzheimer’s, Multiple Sclerosis (MS), and Creutzfeldt-Jakob (Mad Cow Disease). Yeast studies showed that the enzyme that manufactures the lipid is governed by genes FIG4 and VAC14.
Previous studies showed the FIG4 gene is required to maintain normal levels of the signaling lipid ((PI3,5)P2) to maintain a normal nervous system. They also found that humans who had even a minor defect in their FIG4 genes had serious neurological problems.
Those mice missing the VAC14 gene suffer massive neurodegeneration that looks nearly identical to the neurodegeneration seen in the FIG4 mutant mice and the result is the cell bodies of many of the neurons appear to be empty spaces and the brain takes on a spongiform appearance.
In both cases the levels of the lipid–PI(3,5)P2–are one-half the normal level. Because both the VAC14 deficient mice and the FIG4 mutant mice have low levels of the lipid, and both have the same neurodegenerative problems, is evidence that there is a direct link between the lipid and neuronal health.