title: Understanding Pre-Eclampsia Using Alzheimer's Etiology: An Intriguing Viewpoint.
abstract: Characterized by hypertension and proteinuria after the 20th week of gestation, pre-eclampsia (PE) is a major cause of maternal, fetal, and neonatal morbidity and mortality. Despite being recognized for centuries, PE still lacks a reliable, early means of diagnosis or prediction, and a safe and effective therapy. We have recently reported that the event of toxic protein misfolding and aggregation is a critical etiological manifestation in PE. Using comparative proteomic analysis of gestational age-matched sera from PE and normal pregnancy, we identified several proteins that appeared to be dysregulated in PE. Our efforts so far have focused on transthyretin (TTR), a transporter of thyroxine and retinol, and amyloid precursor protein whose aggregates were detected in the PE placenta. Based on these results and detection of TTR aggregates in sera from PE patients, we proposed that PE could be a disease of protein misfolding and aggregation. Protein misfolding and aggregation have long been linked with many neurodegenerative diseases such as Alzheimer's disease. However, linkage of protein misfolding and aggregation with the PE pathogenesis is a new and novel concept. This review aims to understand the roles of aggregated proteins in PE using the cues from the Alzheimer's etiology.
authors.affiliation: Department of Pediatrics, Women and Infants' Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Shi-Bin
authors.initials: SB
authors.lastname: Cheng
authors.affiliation: Department of Pediatrics, Women and Infants' Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Nakashima
authors.affiliation: Department of Pediatrics, Women and Infants' Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Surendra
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000276:immunology*; D000818:Animals; D005260:Female; D011225:Pre-Eclampsia / Q000276:immunology* / Q000473:pathology; D011228:Prealbumin / Q000276:immunology*; D011247:Pregnancy; D066263:Protein Aggregation, Pathological / Q000276:immunology* / Q000473:pathology
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D011228:Prealbumin
keywords: Amyloid precursor protein; autophagy; endoplasmic reticulum stress; pre-eclampsia; protein misfolding and aggregation disease; transthyretin