Endoplasmic reticulum stress and the unfolded protein response: emerging regulators in progression of traumatic brain injury

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(2)

Published: Feb. 20, 2024

Abstract Traumatic brain injury (TBI) is a common trauma with high mortality and disability rates worldwide. However, the current management of this disease still unsatisfactory. Therefore, it necessary to investigate pathophysiological mechanisms TBI in depth improve treatment options. In recent decades, abundant evidence has highlighted significance endoplasmic reticulum stress (ERS) advancing central nervous system (CNS) disorders, including TBI. ERS following leads accumulation unfolded proteins, initiating protein response (UPR). Protein kinase RNA-like ER (PERK), inositol-requiring 1 (IRE1), activating transcription factor 6 (ATF6) are three major pathways UPR initiation that determine whether cell survives or dies. This review focuses on dual effects discusses underlying mechanisms. It suggested may crosstalk series molecular cascade responses, such as mitochondrial dysfunction, oxidative stress, neuroinflammation, autophagy, death, thus involved progression secondary after Hence, promising candidate for

Language: Английский

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Reactive gliosis in traumatic brain injury: a comprehensive review

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 28, 2024

Traumatic brain injury (TBI) is one of the most common pathological conditions impacting central nervous system (CNS). A neurological deficit associated with TBI results from a complex pathogenetic mechanisms including glutamate excitotoxicity, inflammation, demyelination, programmed cell death, or development edema. The critical components contributing to CNS response, damage control, and regeneration after are glial cells–in reaction tissue damage, their activation, hypertrophy, proliferation occur, followed by formation scar. scar creates barrier in damaged helps protect acute phase post-injury. However, this process prevents complete recovery late/chronic producing permanent scarring, which significantly impacts function. Various types participate formation, but mostly attributed reactive astrocytes microglia, play important roles several pathologies. Novel technologies whole-genome transcriptomic epigenomic analyses, unbiased proteomics, show that both microglia represent groups heterogenic subpopulations different genomic functional characteristics, responsible for role neurodegeneration, neuroprotection regeneration. Depending on representation distinct glia subpopulations, as well regenerative processes delayed neurodegeneration may thus differ nearby remote areas structures. This review summarizes process, where resultant effect severity-, region- time-dependent determined model distance explored area lesion site. Here, we also discuss findings concerning intercellular signaling, long-term possibilities novel therapeutical approaches. We believe comprehensive study an emphasis cells, involved post-injury processes, be helpful further research decisive factor when choosing model.

Language: Английский

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How Curcumin Targets Inflammatory Mediators in Diabetes: Therapeutic Insights and Possible Solutions

Molecules, Journal Year: 2022, Volume and Issue: 27(13), P. 4058 - 4058

Published: June 24, 2022

Diabetes mellitus is a multifactorial chronic metabolic disorder, characterized by altered metabolism of macro-nutrients, such as fats, proteins, and carbohydrates. Diabetic retinopathy, diabetic cardiomyopathy, encephalopathy, periodontitis, nephropathy are the prominent complications diabetes. Inflammatory mediators primarily responsible for these complications. Curcumin, polyphenol derived from turmeric, well known its anti-oxidant, anti-inflammatory, anti-apoptotic properties. The regulation several signaling pathways effectively targets inflammatory in Curcumin's anti-inflammatory anti-oxidative activities against wide range molecular have been shown to therapeutic potential variety disorders, including biological examination has that it powerful anti-oxidant stops cells growing releasing active free thiol groups at target location. Curcumin agent diabetes, resistant form leads better outcomes diabetes Moreover, an NF-B inhibitor may be useful treating inhibit diabetes-related enzymes, a-glucosidase, aldose reductase inhibitors. Through effects, suppression vascular endothelial development nuclear transcription factors, curcumin ability prevent, or reduce, course retinopathy. improves insulin sensitivity suppressing phosphorylation ERK/JNK HG-induced insulin-resistant strengthening PI3K-AKT-GSK3B pathway. In present article, we aimed discuss mechanisms regulated various pathways.

Language: Английский

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Michael Acceptors as Anti-Cancer Compounds: Coincidence or Causality?

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 6099 - 6099

Published: June 1, 2024

Michael acceptors represent a class of compounds with potential anti-cancer properties. They act by binding to nucleophilic sites in biological molecules, thereby disrupting cancer cell function and inducing death. This mode action, as well their ability be modified targeted, makes them promising avenue for advancing therapy. We are investigating the molecular mechanisms underlying interactions cells, particular interfere cellular processes induce apoptosis. The properties not accidental but due chemical structure reactivity. electrophilic nature these allows selectively target residues on disease-associated proteins, resulting significant therapeutic benefits minimal toxicity various diseases. opens up new perspectives development more effective precise drugs. Nevertheless, further studies essential fully understand impact our discoveries translate into clinical practice.

Language: Английский

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Exosomes derived from bone marrow mesenchymal stem cells attenuate neurological damage in traumatic brain injury by alleviating glutamate-mediated excitotoxicity

Experimental Neurology, Journal Year: 2022, Volume and Issue: 357, P. 114182 - 114182

Published: July 25, 2022

Language: Английский

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Inflammaging, cellular senescence, and cognitive aging after traumatic brain injury

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 180, P. 106090 - 106090

Published: March 17, 2023

Traumatic brain injury (TBI) is associated with mortality and morbidity worldwide. Accumulating pre-clinical clinical data suggests TBI the leading extrinsic cause of progressive neurodegeneration. Neurological deterioration after either a single moderate-severe or repetitive mild often resembles dementia in aged populations; however, no currently approved therapies adequately mitigate Inflammation correlates neurodegenerative changes cognitive dysfunction for years post-TBI, suggesting potential association between immune activation both age- TBI-induced decline. Inflammaging, chronic, low-grade sterile inflammation natural aging, promotes Cellular senescence subsequent development secretory phenotype (SASP) inflammaging although functional senescent cells neurodegeneration poorly defined TBI. In this mini-review, we provide an overview evidence linking cellular poor outcomes. We also discuss current knowledge future senotherapeutics, including senolytics senomorphics, which kill and/or modulate cells, as therapeutics

Language: Английский

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Impact of curcumin on p38 MAPK: therapeutic implications

Inflammopharmacology, Journal Year: 2023, Volume and Issue: 31(5), P. 2201 - 2212

Published: July 27, 2023

Language: Английский

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Curcumin in the treatment of inflammation and oxidative stress responses in traumatic brain injury: a systematic review and meta-analysis

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

Published: May 10, 2024

Background and aim Traumatic brain injury (TBI), a leading cause of high morbidity mortality, represents significant global public health challenge. Currently, no effective treatment for TBI exists. Curcumin, an active compound extracted from the root Curcuma longa , has demonstrated neuroprotective properties both in vitro vivo . Notably, it shown potential reducing oxidative stress inflammation enhancing redox balance. This paper conducts systematic review meta-analysis to explore curcumin’s role animal models extensively. The findings offer valuable insights future human clinical trials evaluating curcumin as therapeutic supplement or nutraceutical management. Methods Comprehensive literature searches were conducted across MEDLINE, Embase, Cochrane, Web Science, Google Scholar databases. These aimed identify relevant manuscripts all languages, utilizing keywords “curcumin” “traumatic injury.” Results final quantitative analysis included 18 eligible articles corresponding studies. revealed that significantly reduced inflammatory cytokines, including IL-1β ( p = 0.000), IL-6 0.002), TNF-α various concentrations, time points, administration routes. Additionally, markedly enhanced activity markers such SOD Sir2 GPx Nrf2 while MDA 4-HNE 0.001), oxyprotein levels 0.024). Furthermore, improved cerebral edema 0.000) upregulated factors like synapsin I 0.019), BDNF CREB without mNSS 0.144). About autophagy apoptosis, increased Beclin-1 Bcl-2 decreasing caspase-3 apoptosis index P62 0.002). Conclusion Curcumin supplementation positively affects traumatic (TBI) by alleviating responses promoting neuroprotection. It holds agent TBI. However, this conclusion necessitates further substantiation through high-quality additional randomized controlled (RCTs). Systematic Review Registration https://www.crd.york.ac.uk/prospero/ registration number PROSPERO: CRD42023452685.

Language: Английский

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Inhibition of TREM-1 alleviates neuroinflammation by modulating microglial polarization via SYK/p38MAPK signaling pathway after traumatic brain injury

Brain Research, Journal Year: 2024, Volume and Issue: 1834, P. 148907 - 148907

Published: April 1, 2024

Language: Английский

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Therapy of traumatic brain injury by modern agents and traditional Chinese medicine

Chinese Medicine, Journal Year: 2023, Volume and Issue: 18(1)

Published: March 11, 2023

Abstract Traumatic brain injury (TBI) is the leading cause of disability and death, social burden mortality morbidity caused by TBI significant. Under influence comprehensive factors, such as environment, lifestyle, employment type, incidence continues to increase annually. Current pharmacotherapy mainly focuses on symptomatic supportive treatment, aiming reduce intracranial pressure, ease pain, alleviate irritability, fight infection. In this study, we summarized numerous studies covering use neuroprotective agents in different animal models clinical trials after TBI. However, found that no drug has been approved specifically effective for treatment Effective therapeutic strategies remain an urgent need, attention turning toward traditional Chinese medicine. We analyzed reasons why existing high-profile drugs had failed show benefits offered our views research herbal medicine treating

Language: Английский

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