NLRP3 and autophagy in retinal ganglion cell inflammation in age-related macular degeneration: potential therapeutic implications

International Journal of Ophthalmology, Journal Year: 2024, Volume and Issue: 17(8), P. 1531 - 1544

Published: July 24, 2024

Retinal degenerative diseases were a large group of characterized by the primary death retinal ganglion cells (RGCs). Recent studies had shown an interaction between autophagy and nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasomes, which may affect RGCs in diseases. The NLRP3 inflammasome was protein complex that, upon activation, produces caspase-1, mediating apoptosis promoting occurrence development Upregulated could inhibit while inhibited can promote leaded to accelerated emergence drusen lipofuscin deposition under neurosensory retina. activated further autophagy, thus forming vicious cycle that damage RGCs. This review discussed relationship its effects on age-related macular degeneration, providing new perspective direction for treatment

Language: Английский

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Probucol-bile acid based nanoparticles protect auditory cells from oxidative stress: an in vitro study

Therapeutic Delivery, Journal Year: 2024, Volume and Issue: 15(4), P. 237 - 252

Published: March 12, 2024

Aim: Excessive free radicals contribute to oxidative stress and mitochondrial dysfunction in sensorineural hearing loss (SNHL). The antioxidant probucol holds promise, but its limited bioavailability inner ear barriers hinder effective SNHL treatment. Methodology: We addressed this by developing probucol-loaded nanoparticles with polymers lithocholic acid tested them on House Ear Institute-Organ of Corti cells. Results: Probucol-based effectively reduced stress-induced apoptosis, enhanced cellular viability, improved uptake promoted function. Additionally, they demonstrated the capacity reduce reactive oxygen species through nuclear factor erythroid 2-related 2/heme oxygenase-1 pathway. Conclusion: This innovative nanoparticle system potential prevent stress-related impairment, providing an solution for SNHL.

Language: Английский

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Association between oxidative balance score and hearing loss: a cross-sectional study from the NHANES database

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: May 14, 2024

The oxidative balance score (OBS), a composite of dietary nutrients and lifestyles, reflects an individual's antioxidant status. Evidence showed that stress levels were related to hearing loss. relationship between OBS loss remains unclear. This study was explore the association in adults.

Language: Английский

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Nanodelivery of antioxidant Agents: A promising strategy for preventing sensorineural hearing loss

European Journal of Pharmaceutics and Biopharmaceutics, Journal Year: 2024, Volume and Issue: 202, P. 114393 - 114393

Published: July 9, 2024

Language: Английский

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Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(5), P. 1483 - 1494

Published: June 26, 2024

JOURNAL/nrgr/04.03/01300535-202505000-00030/figure1/v/2024-07-28T173839Z/r/image-tiff Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction. However, there are currently no effective pharmacological interventions for patients with noise-induced loss. Here, we present evidence suggesting that lysine-specific demethylase 1 inhibitor–tranylcypromine an otoprotective agent could be used treat loss, and elucidate its underlying regulatory mechanisms. We established a mouse model of permanent threshold shift by exposing mice white broadband noise at sound pressure level 120 dB 4 hours. found tranylcypromine treatment led upregulation Sestrin2 (SESN2) activation autophagy markers light chain 3B lysosome-associated membrane glycoprotein in cochleae treated tranylcypromine. The exposure group showed significantly lower average brainstem response thresholds click, 4, 8, 16 kHz frequencies compared saline. These findings indicate resulted increased SESN2, 3B, expression after exposure, leading reduction levels 4-hydroxynonenal cleaved caspase-3, thereby reducing hair cell Additionally, immunoblot analysis demonstrated upregulated SESN2 via pathway. Tranylcypromine also reduced production NOD-like receptor family pyrin domain-containing 3 (NLRP3) production. In conclusion, our results ameliorated cochlear inflammation promoting which induced autophagy, restricting NLRP3-related inflammasome signaling, alleviating protecting function. suggest inhibiting potential therapeutic strategy preventing

Language: Английский

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Updated insights into the NLRP3 inflammasome in postoperative cognitive dysfunction: emerging mechanisms and treatments

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Sept. 30, 2024

Postoperative cognitive dysfunction (POCD) poses a significant threat to patients undergoing anesthesia and surgery, particularly elderly patients. It is characterized by diminished functions post such as impaired memory decreased concentration. The potential risk factors for POCD include age, surgical trauma, anesthetic type, overall health condition; however, the precise mechanisms underlying remain elusive. Recent studies suggest that neuroinflammation might be primary pathogenic factor. NOD-, LRR- pyrin domain-containing protein 3 (NLRP3) inflammasomes are implicated in exacerbating promoting release of inflammatory proteins initiate pyroptosis, further influencing disease process. regulation NLRP3 inflammasome activity, including its activation degradation, tightly controlled through multiple pathways mechanisms. In addition, autophagy, protective mechanism, regulates control progression POCD. This review reviews recent findings on role pathogenesis discusses therapeutic strategies aimed at reducing sources, inhibiting cellular enhancing autophagy.

Language: Английский

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The significance of serum Klotho to hearing loss: a potential protector under noise pollution

Environmental Science and Pollution Research, Journal Year: 2023, Volume and Issue: 30(47), P. 104464 - 104476

Published: Sept. 13, 2023

Language: Английский

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The role of GDF15 in attenuating noise-induced hidden hearing loss by alleviating oxidative stress

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: Sept. 18, 2024

Language: Английский

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Efficacy and Mechanisms of Antioxidant Compounds and Combinations Thereof Against Cisplatin Induced Hearing Loss in a Rat Model

Published: May 14, 2024

Cisplatin is an election chemotherapeutic agent for many cancer treatments. Its cytotoxicity against neoplastic cells mirrored by that taking place in healthy and tissues, resulting serious adverse events. A very frequent one ototoxicity, causing hearing loss which may permanently affect quality of life after successful oncologic Exacerbated oxidative stress a main cytotoxic mechanism cisplatin, including ototoxicity. Previous reports have shown antioxidant protection cisplatin but there lack comparative studies on the otoprotectant activity formulations. In this paper we report combination vitamins A, C, E Mg++ (ACEMg), previously to protect noise-induced loss, reverses auditory threshold shifts, promotes outer hair cell survival, attenuates cochlea treatment, thus protecting extreme ototoxicity rat. The addition 500 mg N-acetylcysteine (NAC), administered individually also shows significant attenuation ACEMg formulation, results degradation otoprotection. alone, as MgSO4, prevents with NAC, otoprotection greatly degraded. Increasing dose NAC 1000 mg, dramatic compared NAC. These findings support single antioxidants or combinations, particularly experimental series, efficacy However, excess combined and/or elevated doses, above yet be defined “antioxidation threshold”, unrecoverable redox imbalance activity.

Language: Английский

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Noise induces intercellular Ca²⁺signaling waves and the unfolded protein response in the hearing cochlea

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 8, 2024

Abstract Exposure to loud noise is a common cause of acquired hearing loss. Disruption subcellular calcium homeostasis and downstream stress pathways in the endoplasmic reticulum mitochondria, including unfolded protein response, have been implicated pathophysiology noise-induced However, studies on association between has limited due ability measure dynamics mature-hearing, noise-exposed mice. We used genetically encoded indicator mouse model which GcAMP expressed specifically hair cells or supporting under control Myo15Cre Sox2Cre, respectively. performed live imaging UPR gene expression analysis 8-week-old mice exposed levels that cochlear synaptopathy (98 db SPL) permanent loss (106 dB SPL). activation occurred immediately after exposure was dose-dependent, with pro-apoptotic pathway upregulated only 106 exposure. Spontaneous transients intercellular waves cells, are present neonatal cochleae, were quiescent mature-hearing but re-activated upon associated more persistent expansive ICS wave activity. These findings demonstrate strong dose-dependent exposure, activation, changes suggesting targeting these may be effective develop treatments for

Language: Английский

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