Hydroxytyrosol Interference with Inflammaging via Modulation of Inflammation and Autophagy

Nutrients, Journal Year: 2023, Volume and Issue: 15(7), P. 1774 - 1774

Published: April 5, 2023

Inflammaging refers to a chronic, systemic, low-grade inflammation, driven by immune (mainly macrophages) and non-immune cells stimulated endogenous/self, misplaced or altered molecules, belonging physiological aging. This age-related inflammatory status is characterized increased inflammation decreased macroautophagy/autophagy (a degradation process that removes unnecessary dysfunctional cell components). predisposes diseases, including obesity, type-2 diabetes, cancer, cardiovascular neurodegenerative disorders, as well vulnerability infectious diseases vaccine failure, representing thus major target for anti-aging strategies. Phenolic compounds—found in extra-virgin olive oil (EVOO)—are known their beneficial effect on longevity. Among them, hydroxytyrosol (HTyr) appears greatly contribute healthy aging its documented potent antioxidant activity. In addition, HTyr can modulate autophagy, possibly counteracting reducing inflammaging. this review, we reference the literature pure modulatory agent of order highlight possible interference with HTyr-mediated activity might delay development progression related

Language: Английский

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Blockage of Autophagy for Cancer Therapy: A Comprehensive Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7459 - 7459

Published: July 7, 2024

The incidence and mortality of cancer are increasing, making it a leading cause death worldwide. Conventional treatments such as surgery, radiotherapy, chemotherapy face significant limitations due to therapeutic resistance. Autophagy, cellular self-degradation mechanism, plays crucial role in development, drug resistance, treatment. This review investigates the potential autophagy inhibition strategy for cancer. A systematic search was conducted on Embase, PubMed, Google Scholar databases from 1967 2024 identify studies inhibitors their mechanisms therapy. includes original articles utilizing vitro vivo experimental methods, literature reviews, clinical trials. Key terms used were "Autophagy", "Inhibitors", "Molecular mechanism", "Cancer therapy", "Clinical trials". Autophagy chloroquine (CQ) hydroxychloroquine (HCQ) have shown promise preclinical by inhibiting lysosomal acidification preventing autophagosome degradation. Other like wortmannin SAR405 target specific components pathway. Combining these with has demonstrated enhanced efficacy, cells more susceptible cytotoxic agents. Clinical trials involving CQ HCQ encouraging results, although further investigation is needed optimize use exhibits dual cancer, functioning both survival mechanism cell Targeting presents viable therapy, particularly when integrated existing treatments. However, complexity regulation side effects necessitate research develop precise context-specific approaches.

Language: Английский

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Cadmium toxicity and autophagy: a review

BioMetals, Journal Year: 2024, Volume and Issue: 37(3), P. 609 - 629

Published: Jan. 26, 2024

Language: Английский

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PGC-1a mediated mitochondrial biogenesis promotes recovery and survival of neuronal cells from cellular degeneration

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: April 17, 2024

Abstract Neurodegenerative disorders are characterized by the progressive loss of structure and function neurons, often including death neuron. Previously, we reported that, removing cell stimulus, dying/injured neurons could survive recover from process regulated death, even if cells already displayed various signs cellular damage. Now investigated role mitochondrial dynamics (fission/fusion, biogenesis, mitophagy) in both degeneration recovery neuronal cells. In PC12 cells, exposure to ethanol (EtOH) induced massive neurite along with widespread fragmentation, membrane potential loss, reduced ATP production, decreased total volume. By EtOH timely all these parameters recovered normal levels. Meanwhile, regrew neurites survived. Study showed that autophagy was activated only during phase (EtOH treatment) but not removed), it dependent on Parkin/PINK1 mediated mitophagy pathway. Protein expression key regulators fission, phospho-Drp1 Ser616 S-OPA1, increased treatment levels after EtOH. addition, critical PGC-1α biogenesis revealed: inhibition using SR-18292 removal significantly impeded damage, regeneration neurites, survival a concentration-dependent manner. Taken together, our study reversibility morphological functional damage stressed revealed played recovery. This molecular mechanism be target for neuroprotection neurorescue neurodegenerative diseases.

Language: Английский

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Exploring the Prospective Role of Propolis in Modifying Aging Hallmarks

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 390 - 390

Published: Feb. 24, 2024

Aging populations worldwide are placing age-related diseases at the forefront of research agenda. The therapeutic potential natural substances, especially propolis and its components, has led to these products being promising agents for alleviating several cellular molecular-level changes associated with diseases. With this in mind, scientists have introduced a contextual framework guide future aging research, called hallmarks aging. This encompasses various mechanisms including genomic instability, epigenetic changes, mitochondrial dysfunction, inflammation, impaired nutrient sensing, altered intercellular communication. Propolis, rich array bioactive compounds, functions as potent functional food, modulating metabolism, gut microbiota, immune response, offering significant health benefits. Studies emphasize propolis' properties, such antitumor, cardioprotective, neuroprotective effects, well ability mitigate oxidative stress, DNA damage, pathogenic bacteria growth. article underscores current scientific evidence supporting role controlling molecular characteristics linked hallmarks, hypothesizing geroscience research. aim is discover novel strategies improve quality life older individuals, addressing existing deficits perspectives area.

Language: Английский

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Emerging Targets in Amyotrophic lateral sclerosis (ALS): The Promise of ATP-Binding Cassette (ABC) transporter Modulation

Behavioural Brain Research, Journal Year: 2024, Volume and Issue: 476, P. 115242 - 115242

Published: Sept. 6, 2024

Language: Английский

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Physiological functions of ULK1/2

Journal of Molecular Biology, Journal Year: 2024, Volume and Issue: 436(15), P. 168472 - 168472

Published: Feb. 2, 2024

UNC-51-like kinases 1 and 2 (ULK1/2) are serine/threonine that best known for their evolutionarily conserved role in the autophagy pathway. Upon sensing nutrient status of a cell, ULK1/2 integrate signals from upstream cellular energy sensors such as mTOR AMPK relay them to downstream components machinery. also play indispensable roles selective pathway, removing damaged mitochondria, invading pathogens, toxic protein aggregates. Additional functions have emerged beyond autophagy, including trafficking, RNP granule dynamics, signaling events impacting innate immunity, axon guidance, homeostasis, cell fate. Therefore, it is no surprise alterations expression activity been linked with pathophysiological processes, cancer, neurological disorders, cardiovascular diseases. Growing evidence suggests function biological rheostats, tuning intra extra-cellular cues. Given broad physiological relevance, candidate targets small molecule activators or inhibitors may pave way development therapeutics treatment diseases humans.

Language: Английский

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The mechanism of curcumin to protect mouse ovaries from oxidative damage by regulating AMPK/mTOR mediated autophagy

Phytomedicine, Journal Year: 2024, Volume and Issue: 128, P. 155468 - 155468

Published: Feb. 24, 2024

Language: Английский

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Crosstalk Between Autophagy and Oxidative Stress in Hematological Malignancies: Mechanisms, Implications, and Therapeutic Potential

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 264 - 264

Published: Feb. 25, 2025

Autophagy is a fundamental cellular process that maintains homeostasis by degrading damaged components and regulating stress responses. It plays crucial role in cancer biology, including tumor progression, metastasis, therapeutic resistance. Oxidative stress, similarly, key to maintaining balance oxidants antioxidants, with its disruption leading molecular damage. The interplay between autophagy oxidative particularly significant, as reactive oxygen species (ROS) act both inducers by-products of autophagy. While can function suppressor early stages, it often shifts pro-tumorigenic advanced disease, aiding cell survival under adverse conditions such hypoxia nutrient deprivation. This dual mediated several signaling pathways, PI3K/AKT/mTOR, AMPK, HIF-1α, which coordinate the autophagic activity ROS production. In this review, we explore mechanisms interact across different hematological malignancies. We discuss how triggers autophagy, creating feedback loop promotes survival, dysregulation leads increased accumulation, exacerbating tumorigenesis. also examine implications targeting autophagy-oxidative axis cancer. Current strategies involve modulating through specific inhibitors, enhancing levels pro-oxidant compounds, combining these approaches conventional therapies overcome drug Understanding complex relationship provides critical insights into novel aimed at improving treatment outcomes.

Language: Английский

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Decoding microglial immunometabolism: a new frontier in Alzheimer's disease research

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 27, 2025

Abstract Alzheimer’s disease (AD) involves a dynamic interaction between neuroinflammation and metabolic dysregulation, where microglia play central role. These immune cells undergo reprogramming in response to AD-related pathology, with key genes such as TREM2, APOE, HIF-1α orchestrating these processes. Microglial metabolism adapts environmental stimuli, shifting oxidative phosphorylation glycolysis. Hexokinase-2 facilitates glycolytic flux, while AMPK acts an energy sensor, coordinating lipid glucose metabolism. TREM2 APOE regulate microglial homeostasis, influencing Aβ clearance responses. LPL ABCA7, both associated AD risk, modulate processing cholesterol transport, linking neurodegeneration. PPARG further supports by regulating inflammatory Amino acid also contributes function. Indoleamine 2,3-dioxygenase controls the kynurenine pathway, producing neurotoxic metabolites linked pathology. Additionally, glucose-6-phosphate dehydrogenase regulates pentose phosphate maintaining redox balance activation. Dysregulated metabolism, influenced genetic variants APOE4, impair responses exacerbate progression. Recent findings highlight interplay regulators like REV-ERBα, which modulates inflammation, Syk, influences clearance. insights offer promising therapeutic targets, including strategies aimed at modulation, could restore function depending on stage. By integrating metabolic, immune, factors, this review underscores importance of immunometabolism AD. Targeting pathways provide novel for mitigating restoring function, ultimately paving way innovative treatments neurodegenerative diseases.

Language: Английский

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