Understanding Pre-Eclampsia Using Alzheimer's Etiology: An Intriguing Viewpoint

Shi Bin Cheng, Akitoshi Nakashima, Surendra Sharma

Research output: Contribution to journalReview articlepeer-review

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)372-381
Number of pages10
JournalAmerican Journal of Reproductive Immunology
Volume75
Issue number3
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

Keywords

  • Amyloid precursor protein
  • autophagy
  • endoplasmic reticulum stress
  • pre-eclampsia
  • protein misfolding and aggregation disease
  • transthyretin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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