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Published on: January 26, 2024
Protein Misfolding during Pregnancy: New Approaches to Preeclampsia Diagnostics
Elizaveta M Gerasimova1,2, Sergey A Fedotov1,3, Daniel V Kachkin1,2
1Laboratory of Amyloid Biology, St. Petersburg State University, 199034 St. Petersburg, Russia.
Insights
Preeclampsia (PE) diagnosis is challenging due to unclear etiology. Protein misfolding and aggregation are linked to PE, offering potential new diagnostic biomarkers for this pregnancy complication.
Area of Science:
- Obstetrics and Gynecology
- Biochemistry
- Pathology
Background:
- Preeclampsia (PE) is a major global cause of maternal and perinatal mortality.
- Diagnostic challenges persist due to PE's heterogeneous clinical presentation and unclear etiology.
- Recent research links protein misfolding and aggregation to PE pathogenesis.
Purpose of the Study:
- To explore the role of protein aggregation as a potential biomarker for preeclampsia.
- To investigate the association between dysregulated proteins and PE manifestation.
- To identify novel diagnostic approaches for early PE detection.
Main Methods:
- Analysis of protein dysregulation in PE patients.
- Investigation of amyloid-like aggregate deposition in placental tissue and body fluids.
- Exploration of diagnostic techniques like Congo red staining and thioflavin T fluorescence.
Main Results:
- Several proteins (amyloid beta peptide, transthyretin, alpha-1 antitrypsin, albumin, IgG k-free light chains, ceruloplasmin) are dysregulated in PE.
- Toxic, amyloid-like aggregates are deposited in the placenta and body fluids of PE patients.
- Protein aggregation may contribute to defective trophoblast invasion, placental ischemia, and ER stress, promoting PE.
Conclusions:
- Protein aggregation represents an emerging and promising biomarker for preeclampsia.
- Amyloid's unique properties offer avenues for developing novel, rapid diagnostic tests for PE.
- Targeting protein aggregation could lead to improved early diagnosis and management of preeclampsia.
Abstract:
Preeclampsia (PE) is a multisystem heterogeneous complication of pregnancy remaining a leading cause of maternal and perinatal morbidity and mortality over the world. PE has a large spectrum of clinical features and symptoms, which make diagnosis challenging. Despite a long period of studying, PE etiology is still unclear and there are no reliable rapid tests for early diagnosis of this disease. During the last decade, it was shown that proteins misfolding and aggregation are associated with PE. Several proteins, including amyloid beta peptide, transthyretin, alpha-1 antitrypsin, albumin, IgG k-free light chains, and ceruloplasmin are dysregulated in PE, resulting in toxic deposition of amyloid-like aggregates in the placenta and body fluids. It is also possible that aggregated proteins induce defective trophoblast invasion, placental ischemia, ER stress, and promote PE manifestation. The fact that protein aggregation is an emerging biomarker of PE provides an opportunity to develop new diagnostic approaches based on amyloids special features, such as Congo red (CR) staining and thioflavin T (ThT) enhanced fluorescence.
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