Implications of endoplasmic reticulum stress and autophagy in aging and cardiovascular diseases DOI Creative Commons
Chenguang Ma, Yang Liu, Zhiling Fu

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 25, 2024

The average lifespan of humans has been increasing, resulting in a rapidly rising percentage older individuals and high morbidity aging-associated diseases, especially cardiovascular diseases (CVDs). Diverse intracellular extracellular factors that interrupt homeostatic functions the endoplasmic reticulum (ER) induce ER stress. Cells employ dynamic signaling pathway unfolded protein response (UPR) to buffer Recent studies have demonstrated stress triggers various cellular processes associated with aging many including CVDs. Autophagy is conserved process involving lysosomal degradation recycling cytoplasmic components, proteins, organelles, pathogens invade cytoplasm. vital for combating adverse influence on heart. present report summarizes recent mechanism autophagy their overlap CVD pathogenesis context aging. It also discusses possible therapeutic interventions targeting might delay prevent or treat

Language: Английский

Artemisinin Alleviates Astrocyte Overactivation and Neuroinflammation by Modulating the IRE1/NF-κB Signaling Pathway in In Vitro and In Vivo Alzheimer's Disease Models DOI
Lei Chen, Xia Zhao, Rui Sheng

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: 229, P. 96 - 110

Published: Jan. 16, 2025

Language: Английский

Citations

2
The Interplay Between Endoplasmic Reticulum Stress and Ferroptosis in Neurological Diseases DOI

Tianyu Zhai,

Bingbing Wang,

Caizhen Shi

et al.

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(2)

Published: Feb. 10, 2025

Language: Английский

Citations

1
Intracellular Ca2+ signalling: unexpected new roles for the usual suspect DOI Creative Commons
Francesco Moccia, Alessandra Fiorio, Dmitry Lim

et al.

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: July 27, 2023

Cytosolic Ca 2+ signals are organized in complex spatial and temporal patterns that underlie their unique ability to regulate multiple cellular functions. Changes intracellular concentration ([Ca ] i ) finely tuned by the concerted interaction of membrane receptors ion channels introduce into cytosol, -dependent sensors effectors translate elevation [Ca a biological output, -clearing mechanisms return pre-stimulation levels prevent cytotoxic overload. The assortment handling machinery varies among different cell types generate selectively tailored subserve specific advent novel high-speed, 2D 3D time-lapse imaging techniques, single-wavelength genetic indicators, as well development engineering tools manipulate single cells whole animals, has shed light on regulation activity machinery. A symposium within framework 72nd Annual Meeting Italian Society Physiology, held Bari 14–16th September 2022, recently addressed many unexpected whereby signalling regulates fate healthy disease states. Herein, we present report this symposium, which following emerging topics were discussed: 1) Regulation water reabsorption kidney lysosomal release through Transient Receptor Potential Mucolipin 1 (TRPML1); 2) Endoplasmic reticulum-to-mitochondria transfer Alzheimer’s disease-related astroglial dysfunction; 3) non-canonical role TRP Melastatin 8 (TRPM8) Rap1A inhibitor definition some cancer hallmarks; 4) Non-genetic optical stimulation cardiovascular system.

Language: Английский

Citations

14
Methotrimeprazine is a neuroprotective antiviral in JEV infection via adaptive ER stress and autophagy DOI Creative Commons
Surendra Kumar Prajapat, Laxmi Mishra,

Sakshi Khera

et al.

EMBO Molecular Medicine, Journal Year: 2024, Volume and Issue: 16(1), P. 185 - 217

Published: Jan. 2, 2024

Abstract Japanese encephalitis virus (JEV) pathogenesis is driven by a combination of neuronal death and neuroinflammation. We tested 42 FDA-approved drugs that were shown to induce autophagy for antiviral effects. Four in the JE mouse model based on vitro protective effects cell death, inhibition viral replication, anti-inflammatory The antipsychotic phenothiazines Methotrimeprazine (MTP) & Trifluoperazine showed significant survival benefit with reduced titers brain, prevention BBB breach, Both potent mTOR-independent flux inducers. MTP inhibited SERCA channel functioning, induced an adaptive ER stress response diverse types. Pharmacological rescue blocked effect. did not alter translation RNA, but exerted autophagy-dependent effect inhibiting JEV replication complexes. Drug-induced resulted NLRP3 protein levels, attenuation inflammatory cytokine/chemokine release from infected microglial cells. Our study suggests exerts combined infection, has therapeutic potential treatment.

Language: Английский

Citations

5
Identification of therapeutic targets for Alzheimer’s Disease Treatment using bioinformatics and machine learning DOI Creative Commons
Zhongcong Xie, Yongli Situ, Li Deng

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 31, 2025

Alzheimer's disease (AD) is a complex neurodegenerative disorder that currently lacks effective treatment options. This study aimed to identify potential therapeutic targets for the of AD using comprehensive bioinformatics methods and machine learning algorithms. By integrating differential gene expression analysis, weighted co-expression network Mfuzz clustering, single-cell RNA sequencing, algorithms including LASSO regression, SVM-RFE, random forest, five hub genes related AD, PLCB1, NDUFAB1, KRAS, ATP2A2, CALM3 were identified. in particular, exhibited highest diagnostic value showed significant correlation with Braak stages neuronal expression. Furthermore, Noscapine, PX-316, TAK-901 selected as drugs based on PLCB1. research provides reliable method discovery construction models, offering important insights directions future strategies drug development.

Language: Английский

Citations

0
The up-regulation of PTBP1 expression level in patients with Insomnia by senile dementia and promote cuproptosis of nerve cell by SLC31A1 DOI
Jing Wang,

Xiaoli Zhao,

Bin Han

et al.

Sleep Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
The Significance of the Activating Transcription Factor 6 Gene in the Pathogenesis of Drug Resistant Cancer DOI

Ashkan Khanishayan,

Soheila Rahgozar,

Diba Zebardast

et al.

Tissue and Cell, Journal Year: 2025, Volume and Issue: 93, P. 102786 - 102786

Published: Feb. 10, 2025

Language: Английский

Citations

0
SIRT1 Alleviates Oxidative Stress‐Induced Mitochondrial Dysfunction and Mitochondria‐Associated Membrane Dysregulation in Stress Urinary Incontinence DOI Creative Commons
Liying Chen, Jianming Tang, Xiaohu Zuo

et al.

Cell Proliferation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

The pathogenesis of stress urinary incontinence (SUI), a condition common in women, remains to be fully elucidated. This study revealed that the incidence SUI is associated with mitochondrial homeostasis dysregulation following oxidative fibrous connective tissue pelvic floor. SIRT1 an essential factor for maintaining homeostasis; however, its potential role and mechanism action remain unclear. Both vitro vivo, we observed reduced expression inhibit PGC-1α/NRF1/TFAM PINK1/Parkin signalling pathways, eliciting impairment biogenesis mitophagy L929 cells mice. Decreased levels induced endoplasmic reticulum (ER) altered structure mitochondria-associated membranes (MAMs), disrupting ER-mitochondrial calcium exacerbting ROS accumulation. activation can restore function MAMs alleviate ER fibroblasts, promoting anterior vaginal wall repair improving urodynamic parameters model. Our findings provide novel insights into ameliorating stress-induced dysfunction fibroblasts propose as therapeutic target SUI.

Language: Английский

Citations

0
Glycosylation Regulation by TMEM230 in Aging and Autoimmunity DOI Open Access
Eleonora Piscitelli, Edoardo Abeni,

Cristiana Balbino

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2412 - 2412

Published: March 7, 2025

Aging is often a choice between developing cancer or autoimmune disorders, due in part to loss of self-tolerance immunological recognition rogue-acting tumor cells. Self-tolerance and cell by the immune system are processes very much dependent on specific signatures glycans glycosylated factors present plasma membrane stromal components tissue. Glycosylated generated nearly innumerable variations nature, allowing for immensely diverse role these aging flexibility necessary cellular interactions tissue functionality. In previous studies, we showed that differential expression TMEM230, an endoplasmic reticulum (ER) protein was associated with enzymes regulating glycan synthesis processing glycosylation rheumatoid arthritis synovial using single-cell transcript sequencing. this current study, characterize genes pathways co-modulated all types processing, as well glycosylation. Genes biological molecular hallmarks were mitochondria-dependent oxidative phosphorylation reactive oxygen species synthesis, ER-dependent stress unfolded response, DNA repair (UV response P53 signaling pathways), senescence, glycolysis apoptosis regulation through PI3K-AKT-mTOR have been shown play important roles neurodegeneration (such Parkinson’s Alzheimer’s disease). We propose downregulation TMEM230 RNASET2 may represent paradigm study age-dependent disorders their glycosylation, signaling.

Language: Английский

Citations

0
Decoding Alzheimer's Disease With Depression: Molecular Insights and Therapeutic Target DOI Creative Commons
Zekun Li,

Hongmin Guo,

Yihao Ge

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(5)

Published: March 1, 2025

ABSTRACT The purpose of this study was to recognise predictive biomarkers and explore the promising therapeutic targets AD with depression. We confirmed a positive correlation between depression through MR Analysis. Through WGCNA analysis, we identified 1569 genes containing two modules, which were most related AD. In addition, 1629 depressive DEGs also identified. these genes, 84 shared by both depression, screened Degree algorithm, MCC four machine learning algorithms. Two (ITGB5 SPCS1) as AUC > 0.7. Furthermore, nomogram indicated that ITGB5 SPCS1 are good in diagnosing Four drugs targeted at determined DGIdb website. conclusion, for thus providing

Language: Английский

Citations

0