Misfolding linked mutations of SERPINA1 gene are uncommon in preeclampsia

Nagarajappa, Chandrakala; Rangappa, Sheela Shikaripur; Balakrishna, Sharath

doi:10.4103/amhs.amhs_79_19

Cited by 1 publication

(1 citation statement)

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“…An important question is whether any of the known mutations that induce SERPINA1 oligomerization and deficiency exist in PE. Nagarajappa et al conducted a cross-sectional study of 200 preeclamptic women to characterize the frequency of PiS and PiZ mutations, the two dominant mutations in the SERPINA1 gene that cause A1AT deficiency [116]. Results showed that these two variants were non-existent in the study cohort; however, the presence of other unidentified pathogenic mutations cannot be excluded [117].…”

Section: Serpina1/α-1-antitrypsin (A1at)mentioning

confidence: 99%

Protein Misfolding in Pregnancy: Current Insights, Potential Mechanisms, and Implications for the Pathogenesis of Preeclampsia

Medegan Fagla,

Buhimschi

2024

Molecules

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Protein misfolding disorders are a group of diseases characterized by supra-physiologic accumulation and aggregation of pathogenic proteoforms resulting from improper protein folding and/or insufficiency in clearance mechanisms. Although these processes have been historically linked to neurodegenerative disorders, such as Alzheimer’s disease, evidence linking protein misfolding to other pathologies continues to emerge. Indeed, the deposition of toxic protein aggregates in the form of oligomers or large amyloid fibrils has been linked to type 2 diabetes, various types of cancer, and, in more recent years, to preeclampsia, a life-threatening pregnancy-specific disorder. While extensive physiological mechanisms are in place to maintain proteostasis, processes, such as aging, genetic factors, or environmental stress in the form of hypoxia, nutrient deprivation or xenobiotic exposures can induce failure in these systems. As such, pregnancy, a natural physical state that already places the maternal body under significant physiological stress, creates an environment with a lower threshold for aberrant aggregation. In this review, we set out to discuss current evidence of protein misfolding in pregnancy and potential mechanisms supporting a key role for this process in preeclampsia pathogenesis. Improving our understanding of this emerging pathophysiological process in preeclampsia can lead to vital discoveries that can be harnessed to create better diagnoses and treatment modalities for the disorder.

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Section: Serpina1/α-1-antitrypsin (A1at)mentioning

confidence: 99%