Despite improving health care in all areas, scientists have long struggled to determine the cause of a pregnancy complication known as preeclampsia. Though the condition can sometimes be severe, causing seizures, stroke, liver failure, and death, it’s most commonly characterized by proteins in the urine and high blood pressure. Now, a new study is the first to determine the exact types of proteins, and it turns out that some of them are the same ones that are responsible for Alzheimer’s disease.
“Preeclampsia is a very important health problem for women around the world, but for many years no one has understood why or how it happens,” said Dr. Irina Buhimschi, director of the Center for Perinatal Research at the Research Institute of Nationwide Children’s Hospital, in a press release. “We were studying the urine of pregnant women with preeclampsia and noticed these improperly folded proteins, and that was the ‘Eureka!’ moment. It meant that preeclampsia could be similar to other protein misfolding diseases, such as Alzheimer’s and mad cow disease.”
Many protein-folding diseases, or amyloidoses, such as Alzheimer’s, involve the collection of insoluble, densely packed sheeted proteins into plaques that can’t be broken down by enzymes. In Alzheimer’s disease, which is perhaps the most well-known protein-folding disease, beta-amyloid proteins are believed to clog up brain pathways, blocking synapses from making connections, and causing memory loss. Mad cow disease, on the other hand, develops when a protein in the infected cow is eaten, and subsequently moves around the body forcing other naturally occurring proteins in the body to fold upon themselves and become dysfunctional.
The researchers used a dye called Conge Red to test for these proteins as well as any others in the urine of pregnant women. They found that the protein-rich urine contained a variety of proteins: amyloid precursor proteins and enzymes, beta-amyloid, ceruloplasmin, immunoglobin-free light chains, and SERPINA1. They also found a protein known as IFI 6-16, which has been implicated in preventing breast cancer treatment from working.
Buhimschi said that most protein-folding disorders can be traced back to a single protein that’s causing the dysfunction. The team of researchers have already developed a urine test based on the Congo Red dye, called the Congo Red Dot urine test. It can determine whether a woman will develop preeclampsia and how severe it will be. But the new information puts them in a position to determine which protein is responsible for preeclampsia so that they can target it for drug development.
“This would allow us to treat or even prevent preeclampsia symptoms in women who test positive on the Congo Red Dot test,” Buhimschi said. “The story is not over. Preeclampsia may be more than one disease. Particular types may be associated with certain subtypes of protein collections. We want to figure out exactly how each misfolded protein collection affects pregnant women and what we can do about it.”
Source: Buhimschi I, Nayeri U, Zhao G, et al. Protein misfolding, congophilia, oligomerization, and defective amyloid processing in preeclampsia. Science Translational Medicine. 2014.