Sept. 29 (UPI) -- Baylor College of Medicine researchers have discovered that impairing a vital collaboration between brain cells leads to neurodegeneration.
The study, published Thursday in Cell Metabolism, shows the mechanism that two types of brain cells -- neurons and glia -- use to support each other's functions. If the mechanism fails, neurodegeneration occurs.
"Using fruit flies, we are able to thoroughly study the functions of proteins that are shared between flies and humans," Hugo J. Bellen, professor of neuroscience and molecular and human genetics at Baylor College of Medicine and an investigator at the Howard Hughes Medical Institute, said in a news release.
"Often, perturbation of these proteins leads to neurodegenerative characteristics in flies and neurodegenerative diseases in people. By studying how these genes cause defects in fly and mouse models, we can improve our insights into the mechanisms related to human disease."
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Previous studies from the Bellen lab showed that genes involved in neurodegeneration cause damage to neurons and glia by inducing high levels of free radicals, or oxidative stress, and the accumulation of lipid droplets in glia.
"Using electron microscopy, we observed lipid droplet accumulation in glia before obvious symptoms of neurodegeneration," Liu said. "In the presence of high levels of oxidative stress, neurons produce an overabundance of lipids. The combination of free radicals and lipids, which produces peroxidated lipids, is detrimental to cellular health. Neurons try to avoid this damage by secreting these lipids, and apolipoproteins - proteins that transport lipids - carry them to glia cells. Glia store the lipids in lipid droplets, sequestering them from the environment and providing a protective mechanism."
Researchers found that 15 percent of the population carries apolipoprotein APOE4, which is the strongest known genetic risk factor for Alzheimer's disease.
"Meanwhile, APOE2, which is slightly different from APOE4, is protective against the disease," Liu said.
"APOE2 and APOE3 can effectively transfer lipids into glia," Liu said. "On the other hand, APOE4 is practically unable to carry out this process. This results in a lack of lipid droplet accumulation in glia and breakdown of the protective mechanism that sequesters peroxidated lipids. This fundamental difference in the function in APOE4 likely primes an individual to be more susceptible to the damaging effects of oxidative stress, which becomes elevated with age."
