The Probiotic Yeast, Milmed, Promotes Autophagy and Antioxidant Pathways in BV-2 Microglia Cells and C. elegans

Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 393 - 393

Published: March 27, 2025

Background: Autophagy, a catabolic process essential for maintaining cellular homeostasis, declines with age and unhealthy lifestyles, contributing to neurodegenerative diseases. Probiotics, including Milmed yeast, have demonstrated anti-inflammatory antioxidant properties. This study evaluated the activity of on BV-2 microglial cells in vitro vivo model Caenorhabditis elegans (C. elegans) restoring autophagic processes. Methods: were incubated S. cerevisiae (Milmed treated yeast or untreated yeast) then stimulated lipopolysaccharide (LPS). mRNAs factors enzymes assessed by qPCR; mTOR NRF2 ELISA. pNRF2 compared cytosolic was immunofluorescence. The longevity, body size, reactive oxygen species (ROS) levels C. measured fluorescence microscopy. Results: Treatment YPD cultured dried powder obtained from it promoted flux, as shown increased expression Beclin-1, ATG7, LC3, p62 inhibition mTOR, It also enhanced response increasing NRF2, SOD1, GPX; moreover, enhanced, dietary supplementation prolonged survival reduced age-related ROS accumulation without changing gst-4. pro-longevity effect found be dependent SKN-1/Nrf2 activation, absence benefit skn-1 mutants. Conclusions: demonstrates significant pro-autophagy effects elegans, thereby extending lifespan improving stress resistance, which, together previously activity, highlights its role highly effective probiotic beneficial health effects. Activation SKN-1/NRF2 pathway modulation autophagy support therapeutic potential neuroprotection healthy aging.

Language: Английский

Unveiling EXOC4/SEC8: a key player in enhancing antiviral immunity by inhibiting the FBXL19-STING1-SQSTM1 signaling axis

Autophagy, Journal Year: 2025, Volume and Issue: unknown

Published: May 25, 2025

As a core aptamer for anti-DNA viral immunity, STING1 (stimulator of interferon response cGAMP interactor 1) is tightly regulated to ensure the proper functioning natural antiviral immune response. However, many mechanisms underlying regulation remain largely unknown. In this study, we identify EXOC4/SEC8 (exocyst complex component 4) as novel positive regulator DNA virus-triggered type I signaling responses through stabilizing STING1, thereby inhibiting replication. Mechanistically, EXOC4 suppresses K27-linked ubiquitination at K338, K347, and K370 catalyzed by E3 ligase FBXL19 (F-box leucine rich repeat protein 19), preventing ubiquitinated-STING1 from recognition SQSTM1 (sequestosome autophagic degradation. Importantly, mice conditionally knocked out Exoc4/Sec8 are more susceptible herpes simplex virus 1 (HSV-1) infection exhibit severe lung pathology compared control mice. This further confirms important role in immunity. Taken together, our study reveals importance promoting STING1-centered immunity highlights its potential an therapeutic target.

Language: Английский