Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Язык: Английский

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Light-Triggered Nanozymes Remodel the Tumor Hypoxic and Immunosuppressive Microenvironment for Ferroptosis-Enhanced Antitumor Immunity

ACS Nano, Год журнала: 2024, Номер 18(19), С. 12261 - 12275

Опубликована: Апрель 29, 2024

Cancer immunotherapy holds significant promise for addressing diverse malignancies. Nevertheless, its efficacy remains constrained by the intricate tumor immunosuppressive microenvironment. Herein, a light-triggered nanozyme Fe-TCPP-R848-PEG (Fe-MOF-RP) was designed remodeling The Fe-TCPP-MOFs were utilized not only as core catalysis component against destruction but also biocompatible delivery vector of an immunologic agonist, improving long circulation and enrichment. Concurrently, it catalyzes decomposition H2O2 within tumor, yielding oxygen to augment photodynamic therapy. induced ferroptosis, in synergy with therapy, prompts liberation tumor-associated antigens from cells inducing immunogenic cell death. Phototriggered on-demand release R848 agonists stimulated maturation dendritic reverted tumor-promoting M2 phenotypes into adoptive M1 macrophages, which further reshaped Notably, effectively restrains well-established tumors, such B16F10 melanoma. Moreover, demonstrates distal tumor-inhibiting effect upon situ light treatment. What is more, lung metastasis model, elicits robust immune memory, conferring enduring protection rechallenge. Our study presents straightforward broadly applicable strategy crafting nanozymes potential thwart cancer recurrence metastasis.

Язык: Английский

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Oxygen metabolism abnormality and Alzheimer's disease: An update

Redox Biology, Год журнала: 2023, Номер 68, С. 102955 - 102955

Опубликована: Ноя. 8, 2023

Oxygen metabolism abnormality plays a crucial role in the pathogenesis of Alzheimer's disease (AD) via several mechanisms, including hypoxia, oxidative stress, and mitochondrial dysfunction. Hypoxia condition usually results from living high-altitude habitat, cardiovascular cerebrovascular diseases, chronic obstructive sleep apnea. Chronic hypoxia has been identified as significant risk factor for AD, showing an aggravation various pathological components such amyloid β-protein (Aβ) metabolism, tau phosphorylation, dysfunction, neuroinflammation. It is known that excessive hyperoxia can both result stress Oxidative dysfunction increase Aβ proteins lead to redox imbalance, thus forming vicious cycle exacerbating AD pathology. Hyperbaric oxygen therapy (HBOT) non-invasive intervention its capacity significantly enhance cerebral oxygenation levels, which attenuate aggregation, However, further investigation imperative determine optimal pressure, duration exposure, frequency HBOT sessions. In this review, we explore prospects with aim enhancing our understanding underlying molecular mechanisms AD. Current research aimed at attenuating abnormalities holds promise providing novel therapeutic approaches

Язык: Английский

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Hybrid molecules synergistically mitigate ferroptosis and amyloid-associated toxicities in Alzheimer's disease

Redox Biology, Год журнала: 2024, Номер 71, С. 103119 - 103119

Опубликована: Март 11, 2024

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the build-up of extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Ferroptosis, an iron (Fe)-dependent form cell death plays significant role in multifaceted AD pathogenesis through generation reactive oxygen species (ROS), mitochondrial damage, lipid peroxidation, reduction glutathione peroxidase 4 (GPX4) enzyme activity levels. Aberrant liquid-liquid phase separation (LLPS) tau drives growth maturation NFTs contributing to pathogenesis. In this study, we strategically combined structural functional properties gallic acid (GA) cyclic dipeptides (CDPs) synthesize hybrid molecules that effectively target both ferroptosis toxicity AD. This innovative approach marks paradigm shift from conventional therapeutic strategies. first report synthetic small molecule (GCTR) combats ferroptosis, simultaneously restoring enzymatic enhancing cellular levels its master regulator, GPX4. Further, GCTR disrupts Fe3+-induced LLPS tau, aids attenuation abnormal fibrillization. The synergistic action combating toxicity, bolstered GPX4 enhancement modulation LLPS, holds promise for development molecule-based novel therapeutics

Язык: Английский

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Multifunctional Nanocarrier for Synergistic Treatment of Alzheimer’s Disease by Inhibiting β-Amyloid Aggregation and Scavenging Reactive Oxygen Species

ACS Applied Materials & Interfaces, Год журнала: 2024, Номер 16(21), С. 27127 - 27138

Опубликована: Май 15, 2024

The excessive depositions of β-amyloid (Aβ) and abnormal level reactive oxygen species (ROS) are considered as the important pathogenic factors Alzheimer's disease (AD). Strategies targeting only one them have no obvious effects in clinic. In this study, a multifunctional nanocarrier CICe@M-K that crosses blood–brain barrier (BBB) efficiently was developed for inhibiting Aβ aggregation scavenging ROS synchronously. Antioxidant curcumin (Cur) photosensitizer IR780 were loaded mesoporous silica nanomaterials (MSNs). Their surfaces grafted with cerium oxide nanoparticles (CeO2 NPs) short peptide K (CKLVFFAED). Living imaging showed mainly distributed brain, liver, kidneys, indicating crossed BBB accumulated brain. After irradiation 808 nm laser, Cur continuously released. Both can recognize bind to through multiple interaction including π–π stacking interaction, hydrophobic hydrogen bond, aggregation. On other hand, CeO2 NPs cooperate relieve oxidative stress brains by ROS. vivo assays could diminish depositions, alleviate stress, improve cognitive ability APP/PS1 AD mouse model, which demonstrated is potential agent treatment.

Язык: Английский

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Recent Advances in the Inhibition of Membrane Lipid Peroxidation by Food-Borne Plant Polyphenols via the Nrf2/GPx4 Pathway

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(22), С. 12340 - 12355

Опубликована: Май 22, 2024

Lipid peroxidation (LP) leads to changes in the fluidity and permeability of cell membranes, affecting normal cellular function potentially triggering apoptosis or necrosis. This process is closely correlated with onset many diseases. Evidence suggests that phenolic hydroxyl groups food-borne plant polyphenols (FPPs) make them effective antioxidants capable preventing diseases triggered by membrane LP. Proper dietary intake FPPs can attenuate oxidative stress, especially damage phospholipids, activating Nrf2/GPx4 pathway. Nuclear factor E2-related 2 (Nrf2) an stress antagonist. The signaling pathway regulated Nrf2 a defense transduction organism against external stimuli such as reactive oxygen species exogenous chemicals. Glutathione peroxidase 4 (GPx4), under regulation Nrf2, only enzyme reduces lipid peroxides specificity, thus playing pivotal role regulating ferroptosis counteracting stress. study explored mechanism, antioxidant activity FPPs, mechanism It also highlighted bioprotective properties LP its associated mechanisms, including (i) activation pathway, GPx4 serving central target protein, (ii) activities, leading reduction production ROS other peroxides, (iii) effects on downstream phospholipid structure. In conclusion, play crucial natural However, further in-depth analysis coregulation multiple pathways required, combined these mechanisms need evaluation experimental models. Human trials could provide valuable insights into new directions for research application.

Язык: Английский

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Research progress on GPX4 targeted compounds

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 274, С. 116548 - 116548

Опубликована: Май 31, 2024

Язык: Английский

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Insights into IrtAB: Iron Transport Facilitates Ultrasensitive Detection of Mycobacteria in Both Cellular and Clinical Environments

ACS Central Science, Год журнала: 2025, Номер 11(2), С. 261 - 271

Опубликована: Янв. 7, 2025

Mycobacterium tuberculosis (Mtb) utilizes a heterodimeric ABC transporter (IrtAB) to extract Fe3+ ions from host cells. This study demonstrates that ultrasensitive fluorescent probes, achieved through the conjugation of fluorophores with ligand IrtAB, N14G and N14G-Fe can detect smegmatis at concentrations as low 1-10 nM within an incubation period less than 5 min. Furthermore, these probes effectively label bovis Bacille Calmette-Guérin BCG wild-type Mtb strain H37Rv concentration 0.1 μM after 10 min incubation, achieving limit detection 34 Colony-Forming Unit for H37Rv. Both successfully identified in sputum samples patients diagnosed tuberculosis, exhibiting exceptional fluorescence.

Язык: Английский

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Ginger leaf polyphenols mitigate β-amyloid toxicity via JNK/FOXO pathway activation in Caenorhabditis elegans

Food & Function, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Ginger leaf polyphenols (GLP) alleviated β-amyloid toxicity by activating the JNK/FOXO signaling pathway in Caenorhabditis elegans .

Язык: Английский

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The Use of Natural Volatile Compounds on the Fibrillation Domain of Amyloid Beta (GSNKGAIIGLM)─Towards Promising Agents to Combat Alzheimer’s Disease

ACS Chemical Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 9, 2025

Alzheimer's disease (AD), which is caused by the accumulation of amyloid-beta, a major medical concern today. Controlling these aggregates critical to drug development, but delivering them effectively into bloodstream poses significant challenges. In this context, aromatherapy has been proposed as an innovative and promising approach for AD disease. The volatile compounds cinnamaldehyde, phenylethyl alcohol, α-asarone, β-caryophyllene have neuroprotective effects that can be effective in treatment neurodegenerative diseases like AD. amyloid-beta (Aβ) fragment (25–35), retains properties full-length Aβ used suitable model evaluate potential toxicity associated with This study investigated four mentioned at different concentrations on fibrillation process (25–35) peptide. Structural changes peptide analyzed using various techniques such fluorescence probing, far-UV circular dichroism spectroscopy (CD), atomic force microscopy (AFM). Fluorescence probing results showed prevent formation amyloid fibrils forming chemical bonds intermediate species. CD indicated decrease β-sheet content confirmed effect pH structural changes. AFM analysis revealed prevented changed average size intermediates oligomeric These findings show future patients emphasize importance natural prevention diseases.

Язык: Английский

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