Sandra Petersen, veterinary and animal sciences, recently received a two-year, $438,000 exploratory grant from the National Institute of Environmental Health Sciences to further her studies of a little-known gene, CUG RNA-binding protein 2 (CUGBP2), which affects sex-specific development processes in the brain and has been linked to Alzheimer’s disease, neural cell death and reproductive disorders.
She says, “We found previously that CUGBP2 is regulated by both dioxins and estrogens and may be responsible for altering neural processes affected by these substances. We don’t know how CUGBP2 affects neurodevelopment or neurodegeneration, so we want to identify the downstream targets and pathways through which CUGBP2 could act. By identifying the messenger RNAs and proteins – the proximal targets that actually cause cell death – we may have new drug targets for treating or preventing various neural diseases or developmental defects.”
Petersen and colleagues will first use proteomics and genomics techniques to identify proteins regulated by dioxins and estradiol through CUGBP2 in a sex-specific brain region responsible for ovulation. “By identifying these proteins, we may be able to prevent or mitigate actions of neuroendocrine disruptive chemicals that can lead to male infertility, polycystic ovary syndrome and premature ovary failure,” she says.
Further, the gene is one of only a very few associated with late-onset Alzheimer’s disease, which is seen more often in women and not related to the fact that they tend to live longer. Because CUGPB2 regulates neural cell death, the researchers are interested in determining whether estrogen regulation of CUGBP2 during development or in adulthood may contribute to the difference rates of non-age-related Alzheimer’s disease seen in men and women.
Petersen says, “We identified this gene by looking at all the genes that responded differently between males and females and were regulated by both estrogen and dioxin. Using a nonbiased, genomics approach to identify these targets is a very powerful strategy that allows us to make much faster progress in looking at molecular mechanisms than we could before. It sends us in directions we never would have thought to go. There would not have been a reason to investigate this gene without the exploratory genomics results.”