Exploiting sweet relief for preeclampsia by targeting autophagy-lysosomal machinery and proteinopathy

Exploiting sweet relief for preeclampsia by targeting autophagy-lysosomal machinery and proteinopathy

Blog Article

Abstract The etiology of preeclampsia (PE), a severe complication of pregnancy with several clinical manifestations and a high incidence of maternal and fetal morbidity and mortality, remains unclear.This issue is a major hurdle for effective treatment strategies.We recently demonstrated that PE exhibits an Alzheimer-like etiology of impaired autophagy m02n3ll/a and proteinopathy in the placenta.

Targeting of these pathological pathways may be a novel therapeutic strategy for PE.Stimulation of autophagy with the natural disaccharide trehalose and its lacto analog lactotrehalose in hypoxia-exposed primary human trophoblasts restored autophagy, inhibited the accumulation of toxic protein aggregates, and restored the ultrastructural features of autophagosomes and autolysosomes.Importantly, trehalose and lactotrehalose inhibited the onset of PE-like features in a humanized mouse model by normalizing autophagy and inhibiting protein aggregation in the placenta.

These disaccharides restored the autophagy-lysosomal biogenesis machinery by increasing nuclear translocation of the master transcriptional regulator sharps honda TFEB.RNA-seq analysis of the placentas of mice with PE indicated the normalization of the PE-associated transcriptome profile in response to trehalose and lactotrehalose.In summary, our results provide a novel molecular rationale for impaired autophagy and proteinopathy in patients with PE and identify treatment with trehalose and its lacto analog as promising therapeutic options for this severe pregnancy complication.