Investigative Ophthalmology & Visual Science, Год журнала: 2024, Номер 65(11), С. 39 - 39
Опубликована: Сен. 26, 2024
Retinal detachment (RD) leads to photoreceptor (PR) hypoxia due separation from the retinal pigment epithelium (RPE). Hypoxia stabilizes hypoxia-inducible factor 1-alpha (HIF1α), crucial for PR survival during RD. This study explores regulatory role of HIF1α in cell pathways
Язык: Английский
Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)
Опубликована: Июнь 18, 2024
Abstract Background Age-related macular degeneration (AMD) is the leading cause of blindness in elderly people developed world, and number affected expected to almost double by 2040. The retina presents one highest metabolic demands our bodies that partially or fully fulfilled mitochondria neuroretina retinal pigment epithelium (RPE), respectively. Together with its post-mitotic status constant photooxidative damage from incoming light, requires a tightly-regulated housekeeping system involves autophagy. natural polyphenol Urolithin A (UA) has shown neuroprotective benefits several models aging age-associated disorders, mostly attributed ability induce mitophagy mitochondrial biogenesis. Sodium iodate (SI) administration recapitulates late stages AMD, including geographic atrophy photoreceptor cell death. Methods combination vitro, ex vivo were used test potential UA SI model. Functional assays (OCT, ERGs), cellular analysis (flow cytometry, qPCR) fine confocal microscopy (immunohistochemistry, tandem selective autophagy reporters) helped address this question. Results alleviated neurodegeneration preserved visual function SI-treated mice. Simultaneously, we observed severe proteostasis defects upon induction, autophagosome accumulation, resolved animals received UA. Treatment restored autophagic flux triggered PINK1/Parkin-dependent mitophagy, as previously reported literature. Autophagy blockage caused was lysosomal membrane permeabilization. While did not biogenesis, it restore upcycling permeabilized lysosomes through lysophagy. Knockdown lysophagy adaptor SQSTM1/p62 abrogated viability rescue cells, exacerbated inhibited Conclusions Collectively, these data highlight novel putative application treatment AMD whereby bypasses promoting p62-dependent sustain proteostasis. Graphical
Язык: Английский
Процитировано
7
Autophagy, Год журнала: 2024, Номер 20(12), С. 2602 - 2615
Опубликована: Авг. 8, 2024
Aging is a gradual and irreversible physiological process that significantly increases the risks of developing variety pathologies, including neurodegenerative, cardiovascular, metabolic, musculoskeletal, immune system diseases. Mitochondria are energy-producing organelles, their proper functioning crucial for overall cellular health. Over time, mitochondrial function declines causing an increased release harmful reactive oxygen species (ROS) DNA, which leads to oxidative stress, inflammation damage, common features associated with various age-related pathologies. The impairment mitophagy, selective removal damaged or dysfunctional mitochondria by autophagy, relevant development progression molecular mechanisms regulates mitophagy levels in aging remain largely uncharacterized. AMBRA1 intrinsically disordered scaffold protein unique property regulating activity both proliferation autophagy core machineries. While role during embryonic neoplastic transformation has been extensively investigated, its functions post-mitotic cells adult tissues have limited due lethality caused deficiency. Recently, key selectively emerged. Here we summarize discuss these results aim providing comprehensive view roles AMBRA1, how defective functionally linked alterations observed degenerative disorders, muscular dystrophy/sarcopenia, Parkinson diseases, Alzheimer diseases macular degeneration.
Язык: Английский
Процитировано
7
Progress in Retinal and Eye Research, Год журнала: 2024, Номер 101, С. 101264 - 101264
Опубликована: Май 3, 2024
Язык: Английский
Процитировано
6
Trends in Neurosciences, Год журнала: 2023, Номер 46(12), С. 1067 - 1082
Опубликована: Окт. 16, 2023
Язык: Английский
Процитировано
14
Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)
Опубликована: Янв. 6, 2025
The activation of macrophages or microglia in patients' whole body local eyes play significant roles diabetic retinopathy (DR). Mitochondrial function regulates the inflammatory polarization macrophages. Therefore, common mechanism mitochondrial related genes (MRGs) and macrophage polarisation (MPRGs) DR is explored our study to illustrate pathophysiology DR. In this study, using transcriptome data, differentially expressed (DEGs) were firstly analysed for GSE221521, while module MPRGs obtained by weighted gene co-expression network analysis (WGCNA), intersections DEGs with MRGs taken, taken. After that, correlation analyses performed obtain candidate genes. Key Mendelian randomisation (MR) analysis, then biomarkers machine learning combined receiver operating characteristic (ROC) expression validation between control cohorts GSE221521 GSE160306 biomarkers. Finally, subjected immune infiltration set enrichment (GSEA), gene–gene interaction (GGI) analysis. A number 784 taken intersect 1136 782 MPRGs, respectively, after which 89 as MR yielded 13 key clear causal links trends PTAR1 SLC25A34 consistent notable cohort GSE160306. So used Immune showed that activated NK cell Monocyte notably different cohorts, strongest positive correlations cell. Both enriched lysosome insulin signaling pathway. GGI associated prenyltransferase activity prenylation function. This identified two (PTAR1 SLC25A34) explore pathogenesis provide reference targets drug development.
Язык: Английский
Процитировано
0
Medicine, Год журнала: 2025, Номер 104(2), С. e41257 - e41257
Опубликована: Янв. 10, 2025
Background: Bushen-Huoxue-Mingmu-Formula (MMF) has achieved definite clinical efficacy. However, its mechanism is still unclear. Objective: Investigating the molecular of MMF to protect retinal ganglion cells (RGCs). Methods: This study developed a pressurization-induced model damaged RGCs, which were then treated with serum supplemented MMF. The effects on proliferation, apoptosis, adenosine 5′-triphosphate content, and mitochondrial structure RGCs investigated, underlying was explored by RNA interference experiment. Results: In RGC injury model, apoptosis rate increased, cell proliferation decreased, content reduced, disrupted, BCL2-associated X, cleaved caspase-3, microtubule-associated proteins light chain 3 II/I protein expression enhanced, B lymphoma-2 p62 Pink1/Parkin pathway activated. stress-induced damage was, however, reversible following MMF-mediated inhibition pathway. Pink1 short-hairpin downregulated in led outcomes that aligned those observed intervention. Conclusions: altered apoptosis- autophagy-related possibly inhibited signaling pathway, reduced autophagy RGCs. preventive effect can be potentially useful preserve viability
Язык: Английский
Процитировано
0
Chemical Engineering Journal, Год журнала: 2025, Номер 505, С. 159618 - 159618
Опубликована: Янв. 15, 2025
Язык: Английский
Процитировано
0
International Immunopharmacology, Год журнала: 2025, Номер 148, С. 114091 - 114091
Опубликована: Янв. 18, 2025
THSWD has the effect of reducing inflammation, improving microcirculation, and regulating immune status in patients with hepatocellular carcinoma. Regardless its clear therapeutic effect, underlying mechanism action against carcinoma is not clear. To identify critical gut microbiota associated metabolites related to inhibition progression, we assessed microbe-dependent anti-hepatocellular effects through 16 s rRNA gene sequencing, fecal microbial transplantation antibiotic treatment. Metabolic analyses, transcriptomic molecular experiments were performed explore how modulates progression. As confirmed by vivo vitro assays, reduced tumour growth rate promoted apoptosis cells model mice, liver kidney indexes detected safety THSWD. Transcriptomic analysis revealed that targets significantly enriched multiple lysosomal autophagy signalling pathways, suggesting probably THSWD's effect. Based on integrated data analysis, delays progression increasing intestinal Duncaniella augmenting metabolite glabrol, joint metabolic genomic suggests this autophagy, cellular The differential glabrol induces triggering autophagy-mediated pathway. Supplementation up regulates LTF/AMPK/mTOR/Beclin1 axis promotes induced cells.
Язык: Английский
Процитировано
0
Life Sciences in Space Research, Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0
Journal of Molecular Biology, Год журнала: 2025, Номер unknown, С. 169105 - 169105
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0