Polydatin reactivates mitochondrial bioenergetics and mitophagy while preventing premature senescence by modulating microRNA-155 and its direct targets in human fibroblasts with trisomy 21 DOI Creative Commons
Daniela Valenti, Daniela Isabel Abbrescia, Flaviana Marzano

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Mitochondrial dysfunction and redox dyshomeostasis are considered crucial factors causally linked to the pathogenesis of Down syndrome (DS), a human genetic anomaly currently lacking cure, associated with neurodevelopmental deficits in children early onset symptoms aging adults. Several natural plant-derived polyphenolic compounds, known for their neurostimulator, antioxidant anti-inflammatory activities, have been proposed as dietary supplements manage DS-linked phenotypic alterations. However, poor bioavailability rapid metabolism these compounds limited conclusive evidence regarding clinical efficacy individuals DS. Polydatin (PLD), glucoside precursor resveratrol derived from Polygonum cuspidatum, is instead highly bioavailable resistant enzymatic oxidation. PLD supplementation has shown many therapeutic efficacies several diseases without side effects. In this study, we used fetal trisomy 21 skin fibroblasts (DS-HSFs) investigate, mechanistic point view, whether could prevent or counteract critical cellular alterations both Our findings demonstrate that reactivates mitochondrial bioenergetics, reduces oxygen radical overproduction prevents oxidative stress (OS)-induced senescence DNA damage DS-HSF. Notably, identified novel mechanism action involving chromosome-21-encoded microRNA-155 (miR-155) its direct target genes casitas B-lineage lymphoma (CBL), BAG Cochaperone 5 (BAG5) transcription factor A (TFAM). These proteins play pivotal roles regulating biogenesis mitophagy. Given deregulation miR-155/CBL axis also implicated acute leukemias, which frequently occur DS, emerges promising candidate translational application. Its ability enhance bioenergetics address DS-associated highlights potential.

Language: Английский

Role of cystathionine-β-synthase and hydrogen sulfide in down syndrome DOI Creative Commons
Csaba Szabó

Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. e00584 - e00584

Published: April 1, 2025

Language: Английский

Citations

0
Polydatin reactivates mitochondrial bioenergetics and mitophagy while preventing premature senescence by modulating microRNA-155 and its direct targets in human fibroblasts with trisomy 21 DOI Creative Commons
Daniela Valenti, Daniela Isabel Abbrescia, Flaviana Marzano

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Mitochondrial dysfunction and redox dyshomeostasis are considered crucial factors causally linked to the pathogenesis of Down syndrome (DS), a human genetic anomaly currently lacking cure, associated with neurodevelopmental deficits in children early onset symptoms aging adults. Several natural plant-derived polyphenolic compounds, known for their neurostimulator, antioxidant anti-inflammatory activities, have been proposed as dietary supplements manage DS-linked phenotypic alterations. However, poor bioavailability rapid metabolism these compounds limited conclusive evidence regarding clinical efficacy individuals DS. Polydatin (PLD), glucoside precursor resveratrol derived from Polygonum cuspidatum, is instead highly bioavailable resistant enzymatic oxidation. PLD supplementation has shown many therapeutic efficacies several diseases without side effects. In this study, we used fetal trisomy 21 skin fibroblasts (DS-HSFs) investigate, mechanistic point view, whether could prevent or counteract critical cellular alterations both Our findings demonstrate that reactivates mitochondrial bioenergetics, reduces oxygen radical overproduction prevents oxidative stress (OS)-induced senescence DNA damage DS-HSF. Notably, identified novel mechanism action involving chromosome-21-encoded microRNA-155 (miR-155) its direct target genes casitas B-lineage lymphoma (CBL), BAG Cochaperone 5 (BAG5) transcription factor A (TFAM). These proteins play pivotal roles regulating biogenesis mitophagy. Given deregulation miR-155/CBL axis also implicated acute leukemias, which frequently occur DS, emerges promising candidate translational application. Its ability enhance bioenergetics address DS-associated highlights potential.

Language: Английский

Citations

0