The Ubiquitin–Proteasome System in Immune Cells

Biomolecules, Год журнала: 2021, Номер 11(1), С. 60 - 60

Опубликована: Янв. 5, 2021

The ubiquitin–proteasome system (UPS) is the major intracellular and non-lysosomal protein degradation system. Thanks to its unique capacity of eliminating old, damaged, misfolded, and/or regulatory proteins in a highly specific manner, UPS virtually involved almost all aspects eukaryotic life. critical importance particularly visible immune cells which undergo rapid profound functional remodelling upon pathogen recognition. Innate adaptive activation indeed characterized by number substantial changes impacting various cellular processes including homeostasis, signal transduction, cell proliferation, antigen processing are tightly regulated UPS. In this review, we summarize discuss recent progress our understanding molecular mechanisms contributes generation an adequate response. regard, also consequences dysfunction role pathogenesis recently described disorders cancer auto-inflammatory diseases.

Язык: Английский

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Quadruple abnormal protein aggregates in brainstem pathology and exogenous metal-rich magnetic nanoparticles (and engineered Ti-rich nanorods). The substantia nigrae is a very early target in young urbanites and the gastrointestinal tract a key brainstem portal

Environmental Research, Год журнала: 2020, Номер 191, С. 110139 - 110139

Опубликована: Сен. 1, 2020

Язык: Английский

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The proteasome and its role in the nervous system

Cell chemical biology, Год журнала: 2021, Номер 28(7), С. 903 - 917

Опубликована: Апрель 26, 2021

Язык: Английский

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TDP-43 pathology: From noxious assembly to therapeutic removal

Progress in Neurobiology, Год журнала: 2022, Номер 211, С. 102229 - 102229

Опубликована: Янв. 29, 2022

Язык: Английский

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BAG3 Overexpression Attenuates Ischemic Stroke Injury by Activating Autophagy and Inhibiting Apoptosis

Stroke, Год журнала: 2023, Номер 54(8), С. 2114 - 2125

Опубликована: Июнь 28, 2023

The ubiquitin-proteasome system (UPS) and autophagy are 2 major protein degradation pathways in eukaryotic cells. We previously identified a switch from UPS to with changes BAG3 (B-cell lymphoma 2-associated-athanogene 3) expression after cerebral ischemia mice. is an antiapoptotic-cochaperone that directly involved cellular quality control as mediator for selective macroautophagy. Here, we aimed investigate the role of ischemic stroke.Middle artery occlusion/reperfusion (MCAO/R) oxygen-glucose deprivation/reoxygenation were used mimic vivo vitro. inhibitor MG132 3-MA (3-methyladenine) administered mice identify how was MCAO/R. Adeno-associated virus lentiviral vector regulate vitro, respectively. Behavioral tests, 2,3,5-triphenyltetrazolium chloride staining, Hematoxylin & Eosin staining performed evaluate injury following MCAO/R, Cell Counting kit-8 assay conducted assess deprivation/reoxygenation-induced Brain tissues cell lysates collected analyzed activation, autophagy, apoptosis.The alleviated MCAO increased expression, whereas exacerbated MCAO/R-induced injury. In addition, overexpression significantly improved neurological outcomes, reduced infarct volume vivo, enhanced survival by activating suppressing apoptosis vitro.Our findings indicate activates inhibits prevent ischemia/reperfusion hypoxia/reoxygenation injury, suggesting potential therapeutic benefit ischemia.

Язык: Английский

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Proteostasis failure exacerbates neuronal circuit dysfunction and sleep impairments in Alzheimer’s disease

Molecular Neurodegeneration, Год журнала: 2023, Номер 18(1)

Опубликована: Апрель 21, 2023

Abstract Failed proteostasis is a well-documented feature of Alzheimer’s disease, particularly, reduced protein degradation and clearance. However, the contribution failed to neuronal circuit dysfunction an emerging concept in neurodegenerative research will prove critical understanding cognitive decline. Our objective convey disease progression with growing evidence for bidirectional relationship sleep disruption failure. Proteostasis tauopathy disrupts neurons that regulate sleep–wake cycle, which presents behavior as impaired slow wave rapid eye movement patterns. Subsequent loss further impairs Sleep defined seen early many disorders contributes memory impairments disease. Canonical pathological hallmarks, β-amyloid, tau, directly disrupt sleep, neurodegeneration locus coeruleus, hippocampal hypothalamic from tau proteinopathy causes circuitry sleep. Acting positive-feedback-loop, circadian rhythm then increase spread β-amyloid through proteasome, autophagy, unfolded response glymphatic This phenomenon extends beyond interactions impairment homeostasis TDP-43, α-synuclein, FUS, huntingtin proteins, implicating important consideration array diseases cases mixed neuropathology. Critically, dynamics this interaction environment are not fully elucidated deserving discussion research. Finally, we propose sleep-enhancing therapeutics potential interventions promoting healthy proteostasis, including clearance, mechanistically linking these processes. With clinical preclinical research, dynamic diagnostic therapeutic framework, informing precise single- combinatorial-treatments other brain disorders. Graphical

Язык: Английский

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Activation of α7nAch receptors ameliorates α-synuclein pathology in the brain and gut of a subacute MPTP mouse model of Parkinson's disease

Biomedicine & Pharmacotherapy, Год журнала: 2025, Номер 184, С. 117871 - 117871

Опубликована: Фев. 1, 2025

Язык: Английский

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Resveratrol-Enhanced Human Neural Stem Cell-Derived Exosomes Mitigate MPP+-Induced Neurotoxicity Through Activation of AMPK and Nrf2 Pathways and Inhibition of the NLRP3 Inflammasome in SH-SY5Y Cells

Life, Год журнала: 2025, Номер 15(2), С. 294 - 294

Опубликована: Фев. 13, 2025

Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily characterized by the loss of dopaminergic neurons in substantia nigra. Mitochondrial dysfunction, oxidative stress, and neuroinflammation are recognized as critical pathological mechanisms driving neurodegeneration PD. Exosome (Exo)-based therapies, particularly those derived from human neural stem cells (hNSCs), offer promising neuroprotective effects due to their ability transfer bioactive molecules that modulate cellular processes. Resveratrol (RES), polyphenolic compound with potent antioxidant anti-inflammatory properties, has been shown enhance therapeutic potential cell (SC)-derived Exos. This study investigated RES-treated hNSCs-derived Exos (RES-hNSCs-Exos) on SH-SY5Y exposed 1-methyl-4-phenylpyridinium (MPP+), neurotoxin commonly used model Parkinsonian neurotoxicity. Treating MPP+ led significant reductions viability, mitochondrial increased activation inflammatory pathways. Treatment RES-hNSCs-Exos rescued MPP+-induced toxicity improving enhancing ATP production, increasing biogenesis, reducing reactive oxygen species (ROS) generation. The findings also demonstrated expression essential genes involved such PGC1α, NRF1, Tfam, indicating improved function presence RES-hNSCs-Exos. Further analysis revealed these protective were mediated activating AMP-activated protein kinase (AMPK) Nrf2 signaling pathways, which promoted health reduced stress. Moreover, treatment suppressed downregulating NLRP3 inflammasome secretion pro-inflammatory cytokines IL-1β IL-18. In conclusion, results suggest exhibit against neurotoxicity function, inhibiting neuroinflammation. These highlight hNSCs-Exos novel strategy for diseases like PD, RES valuable enhancer efficacy.

Язык: Английский

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Ubiquitin signaling in neurodegenerative diseases: an autophagy and proteasome perspective

Cell Death and Differentiation, Год журнала: 2020, Номер 28(2), С. 439 - 454

Опубликована: Ноя. 18, 2020

Язык: Английский

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Merging the Multi-Target Effects of Phytochemicals in Neurodegeneration: From Oxidative Stress to Protein Aggregation and Inflammation

Antioxidants, Год журнала: 2020, Номер 9(10), С. 1022 - 1022

Опубликована: Окт. 20, 2020

Wide experimental evidence has been provided in the last decade concerning neuroprotective effects of phytochemicals a variety neurodegenerative disorders. Generally, bioactive compounds belonging to different phytochemical classes are attributed antioxidant, anti-aggregation, and anti-inflammatory activity along with restoration mitochondrial homeostasis targeting alterations cell-clearing systems. Far from being independent, these multi-target represent interconnected events that commonly implicated pathogenesis most diseases, independently etiology, nosography, specific misfolded proteins involved. Nonetheless, increasing amount data applying disorders joined multiple exerted by wide plant-derived agents may rather confound reader. The present review is an attempt provide general guideline about relevant mechanisms through which naturally occurring counteract neurodegeneration. With such aim, we focus on some popular as representative examples design sort main highway aimed at deciphering protective make potentially useful counteracting In this frame, emphasize potential role machinery kernel anti-inflammatory, protecting phytochemicals.

Язык: Английский

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