Brain Iron Metabolism, Redox Balance and Neurological Diseases

Antioxidants, Journal Year: 2023, Volume and Issue: 12(6), P. 1289 - 1289

Published: June 16, 2023

The incidence of neurological diseases, such as Parkinson’s disease, Alzheimer’s disease and stroke, is increasing. An increasing number studies have correlated these diseases with brain iron overload the resulting oxidative damage. Brain deficiency has also been closely linked to neurodevelopment. These disorders seriously affect physical mental health patients bring heavy economic burdens families society. Therefore, it important maintain homeostasis understand mechanism affecting reactive oxygen species (ROS) balance, in neural damage, cell death and, ultimately, leading development disease. Evidence shown that many therapies targeting ROS imbalances good preventive therapeutic effects on diseases. This review highlights molecular mechanisms, pathogenesis treatment strategies metabolism

Language: Английский

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Metal–Organic Frameworks‐Based Nanoplatforms for the Theranostic Applications of Neurological Diseases

Small, Journal Year: 2023, Volume and Issue: 19(23)

Published: March 12, 2023

Abstract Neurological diseases are the foremost cause of disability and second leading death worldwide. Owing to special microenvironment neural tissues biological characteristics cells, a considerable number neurological disorders currently incurable. In past few years, development nanoplatforms based on metal–organic frameworks (MOFs) has broadened opportunities for offering sensitive diagnosis/monitoring effective therapy neurology‐related diseases. this article, obstacles neurotherapeutics, including delayed diagnosis misdiagnosis, existence blood brain barrier (BBB), off‐target treatment, irrepressible inflammatory storm/oxidative stress, irreversible nerve cell summarized. Correspondingly, MOFs‐based diagnostic/monitoring strategies such as neuroimaging biosensors (electrochemistry, fluorometry, colorimetry, electrochemiluminescence, etc.) therapeutic higher BBB permeability, targeting specific lesion sites, attenuation neuroinflammation/oxidative stress well regeneration extensively highlighted management Finally, challenges present research from perspective clinical translation discussed, hoping facilitate interdisciplinary studies at intersections between neurotheranostics.

Language: Английский

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Rapamycin reverses ferroptosis by increasing autophagy in MPTP/MPP+-induced models of Parkinson’s disease

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 18(11), P. 2514 - 2519

Published: March 11, 2023

Parkinson's disease is a neurodegenerative disorder, and ferroptosis plays significant role in the pathological mechanism underlying disease. Rapamycin, an autophagy inducer, has been shown to have neuroprotective effects However, link between rapamycin not entirely clear. In this study, was administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model 1-methyl-4-phenylpyridinium-induced PC12 cell model. The results showed that improved behavioral symptoms of mice, reduced loss dopamine neurons substantia nigra pars compacta, expression ferroptosis-related indicators (glutathione peroxidase 4, recombinant solute carrier family 7, member 11, glutathione, malondialdehyde, reactive oxygen species). model, viability ferroptosis. effect attenuated by inducer (methyl (1S,3R)-2-(2-chloroacetyl)-1-(4-methoxycarbonylphenyl)-1,3,4,9-tetrahyyridoindole-3-carboxylate) inhibitor (3-methyladenine). Inhibiting activating may be important which exerts its effects. Therefore, regulation provide therapeutic target for drug treatments

Language: Английский

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Novel druggable mechanism of Parkinson's disease: Potential therapeutics and underlying pathogenesis based on ferroptosis

Medicinal Research Reviews, Journal Year: 2023, Volume and Issue: 43(4), P. 872 - 896

Published: March 16, 2023

Genetics, age, environmental factors, and oxidative stress have all been implicated in the development of Parkinson's disease (PD); however, a complete understanding its pathology remains elusive. At present, there is no cure for PD, currently available therapeutics are insufficient to meet patient needs. Ferroptosis, distinctive iron-dependent cell death mode characterized by lipid peroxidation stress, has pathophysiological features similar those including iron accumulation, reactive oxygen species-induced damage, mitochondrial dysfunction. Ferroptosis identified as specific pathway neuronal closely related pathogenesis PD. Despite similarities biological targets involved PD ferroptosis, relationship between novel ferroptosis neglected literature. In this review, mechanism discussed, potential therapeutic both compared. Furthermore, anti-PD effects several inhibitors, well clinical studies thereof, identification lead compounds treatment inhibition reviewed. It hoped that review can promote research further elucidate provide new strategies ferroptosis-targeting therapy.

Language: Английский

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Biomineralization-Tuned Nanounits Reprogram the Signal Transducer and Activator of Transcription 3 Signaling for Ferroptosis-Immunotherapy in Cancer Stem Cells

ACS Nano, Journal Year: 2024, Volume and Issue: 18(32), P. 21268 - 21287

Published: July 31, 2024

Cancer stem cells (CSCs) are promising targets for improving anticancer treatment outcomes while eliminating recurrence, but their remains a major challenge. Here, we report nanointegrative strategy to realize CSC-targeted ferroptosis-immunotherapy through spatiotemporally controlled reprogramming of STAT3-regulated signaling circuits. Specifically, STAT3 inhibitor niclosamide (Ni) and an experimental ferroptosis drug (1S, 3R)-RSL3 (RSL3) integrated into hyaluronic acid-modified amorphous calcium phosphate (ACP) nanounits biomineralization (CaP-PEG-HA@Ni/RSL3), which could be recognized by CD44-overexpressing CSCs released in synchronized manner. Ni inhibits the CSC-intrinsic STAT3-PD-L1 axis stimulate adaptive immunity enhance interferon gamma (IFNγ) secretion CD8+ T downregulate SLC7A11 SLC3A2 blocking glutathione biosynthesis. Meanwhile, Ni-dependent inhibition also upregulates ACSL4 downstream IFNγ feedback. These effects cooperate with RSL3-mediated GPX4 deactivation induce pronounced ferroptosis. Furthermore, CaP-PEG-HA@Ni/RSL3 impairs immunosuppressive M2-like tumor-associated macrophages, Ca2+ ions from degraded ACP chelate lipid peroxides ferroptotic avoid T-cell inhibition, thus boosting effector function activated cells. This study offers cooperative ferroptosis-immunotherapeutic approach refractory cancer.

Language: Английский

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