Visualizing Endoplasmic Reticulum Stress and Autophagy in Alzheimer’s Model Cells by a Peroxynitrite-Responsive AIEgen Fluorescent Probe

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: 16(2), P. 223 - 231

Published: Jan. 7, 2025

Endoplasmic reticulum (ER) stress and autophagy (ER-phagy) occurring in nerve cells are crucial physiological processes closely associated with Alzheimer's disease (AD). Visualizing the two is paramount to advance our understanding of AD pathologies. Among biomarkers identified, peroxynitrite (ONOO-) emerges as a key molecule initiation aggravation ER ER-phagy, highlighting its significance underlying mechanisms processes. In this work, we designed synthesized an innovative ONOO--responsive AIEgen-based fluorescent probe (DHQM) ability monitor ER-phagy model cells. DHQM demonstrated excellent aggregation-induced emission (AIE) properties, endowing it outstanding for washing-free intracellular imaging. Meanwhile, exhibited high sensitivity, remarkable selectivity ONOO-, exceptional ER-targeting ability. The was successfully applied fluorescence imaging ONOO- fluctuations assess status aluminum-induced Our findings revealed that ferroptosis, regulated cell death process, pivotal excessive production, which turn activated exacerbated stress. Furthermore, aluminum-stimulated observed utilizing DHQM, might be inhibiting ferroptosis mitigating aberrant Overall, study not only offers valuable insights into pathological at level but also opens new potential therapeutic avenues targeting these pathways.

Language: Английский

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Brucella suis S2 strain inhibits IRE1/caspase-12/caspase-3 pathway-mediated apoptosis of microglia HMC3 by affecting the ubiquitination of CALR

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

Published: Feb. 28, 2025

ABSTRACT Neurobrucellosis represents a severe complication of brucellosis, posing considerable risk to human health and quality life. This condition arises from an increased susceptibility chronic Brucella infection, significant clinical challenge. One key factor contributing neurobrucellosis is the regulation microglial apoptosis by ; however, exact molecular mechanisms remain largely unresolved. In this study, clone 3 (HMC3) cells were infected with suis vaccine strain S2 ( B. S2) at varying multiplicity infection (MOI) durations assess its effects on IRE1/caspase-12/caspase-3 signaling pathway. Following suppression pathway S2, calreticulin (CALR) was identified through ubiquitin-modified proteomics (data accessible via ProteomeXchange, identifier PXD056006). To further investigate, CALR-overexpression knockdown HMC3 cell lines elucidate mechanism which inhibits in cells. conclusion, our findings demonstrate that suppresses modulating CALR ubiquitination. study provides theoretical basis for exploring offers insights into treatment. IMPORTANCE impacting central nervous system (CNS) due neurological deficits caused , primary features including meningitis, encephalitis, brain abscesses, demyelinating lesions. These nonspecific symptoms often lead misdiagnosis or delayed diagnosis, increasing recurrent infections. Consequently, persistent relapse are critical challenges management neurobrucellosis, closely linked ’s survival replication within microglia. Interestingly, may inhibit microglia mitigating endoplasmic reticulum (ER) stress, though precise unexplored. Thus, will specific provide deeper pathogenesis treatment neurobrucellosis.

Language: Английский

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Ferroptosis: a novel mechanism of cell death in ophthalmic conditions

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

Published: June 27, 2024

Ferroptosis, a new type of programmed cell death proposed in recent years, is characterized mainly by reactive oxygen species and iron-mediated lipid peroxidation differs from death, such as apoptosis, necrosis, autophagy. Ferroptosis associated with variety physiological pathophysiological processes. Recent studies have shown that ferroptosis can aggravate or reduce the occurrence development diseases targeting metabolic pathways signaling tumors, ischemic organ damage, other degenerative related to peroxidation. Increasing evidence suggests closely linked onset progression various ophthalmic conditions, including corneal injury, glaucoma, age-related macular degeneration, diabetic retinopathy, retinal detachment, retinoblastoma. Our review current research on reveals significant advancements our understanding pathogenesis, aetiology, treatment these conditions.

Language: Английский

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Dual-State Emissive Mitochondrial Viscosity Probe for Long-Term Imaging of Rheumatoid Arthritis

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Rheumatoid arthritis (RA) is a destructive autoimmune disease that seriously affects human health. Due to the lack of cure for RA, good prognosis largely depends on early diagnosis and effective treatment monitoring RA. Therefore, development fluorescent probes capable real-time detection RA great significance. Dual-state emission (DSE) molecules can emit light in both dilute solution solid state, making them ideal fluorophores constructing probes. However, there are currently no reports DSE molecule-based imaging. Herein, we report probe MQP-Boc based novel molecule selectively responds viscosity with sensitive fluorescence changes at 667 nm mitochondria targetable. Cell imaging studies show detect mitochondrial perform long-term mitochondria, which significantly superior control MQP-Ac. Imaging mouse model induced by λ-carrageenan has excellent capabilities Besides, MQP-Boc, significant increases joint tissue were found during process. All results indicate an new tool studying diagnosing

Language: Английский

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Reaction-based small-molecule fluorescent probes for endoplasmic reticulum- and mitochondria-targeted biosensing and bioimaging

Science China Materials, Journal Year: 2024, Volume and Issue: 67(11), P. 3491 - 3530

Published: Oct. 17, 2024

Language: Английский

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Discovery of Coumarins from Zanthoxylum dimorphophyllum var. spinifoliumas and Their Potential against Rheumatoid Arthritis

Molecules, Journal Year: 2024, Volume and Issue: 29(18), P. 4395 - 4395

Published: Sept. 16, 2024

In the present study, a series of coumarins, including eight undescribed bis-isoprenylated ones Spinifoliumin A-H, were isolated and identified from aerial parts

Language: Английский

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Unveiling ferroptosis: a new frontier in skin disease research

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

Published: Oct. 4, 2024

Ferroptosis, a form of regulated cell death distinct from apoptosis, necrosis, and autophagy, is increasingly recognized for its role in skin disease pathology. Characterized by iron accumulation lipid peroxidation, ferroptosis has been implicated the progression various conditions, including psoriasis, photosensitive dermatitis, melanoma. This review provides an in-depth analysis molecular mechanisms underlying compares cellular effects with other forms context health disease. We systematically examine five specific diseases, ichthyosis, polymorphous light eruption (PMLE), vitiligo, melanoma, detailing influence on pathogenesis progression. Moreover, we explore current clinical landscape ferroptosis-targeted therapies, discussing their potential managing treating diseases. Our aim to shed therapeutic modulating research practice.

Language: Английский

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