Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 2, 2025

Язык: Английский

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Iron toxicity, ferroptosis and microbiota in Parkinson’s disease: Implications for novel targets

Advances in neurotoxicology, Год журнала: 2024, Номер unknown, С. 105 - 132

Опубликована: Янв. 1, 2024

Язык: Английский

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Targeting the Labile Iron Pool with Engineered DFO Nanosheets to Inhibit Ferroptosis for Parkinson's Disease Therapy

Advanced Materials, Год журнала: 2024, Номер 36(41)

Опубликована: Сен. 2, 2024

Ferroptosis in neurons is considered one of the key factors that induces Parkinson's disease (PD), which caused by excessive iron accumulation intracellular labile pool (LIP). The ions released from LIP lead to aberrant generation reactive oxygen species (ROS) trigger ferroptosis and exacerbate PD progression. Herein, a pioneering design multifunctional nanoregulator deferoxamine (DFO)-integrated nanosheets (BDPR NSs) presented target restrict protect against PD. BDPR NSs are constructed incorporating brain-targeting peptide DFO into polydopamine-modified black phosphorus nanosheets. These can sequester free ions, thereby ameliorating overload regulating metabolism. Furthermore, decrease lipid peroxidation mitigating ROS accumulation. More importantly, specifically accumulate mitochondria suppress mitochondrial In vivo experiments demonstrated highly efficiently mitigated dopaminergic neuronloss its associated behavioral disorders modulating inhibiting ferroptosis. Thus, BDPR-based nanovectors holds promise as potential avenue for advancing therapy.

Язык: Английский

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High-fat diet exacerbates 1-Bromopropane-induced loss of dopaminergic neurons in the substantia nigra of mice through mitochondrial damage associated necroptotic pathway

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 276, С. 116280 - 116280

Опубликована: Апрель 3, 2024

In recent years, accumulating evidence supports that occupational exposure to solvents is associated with an increased incidence of Parkinson's disease (PD) among workers. The neurotoxic effects 1-bromopropane (1-BP), a widely used new-type solvent, are well-established, yet data on its relationship the etiology PD remain limited. Simultaneously, high-fat consumption in modern society recognized as significant risk factor for PD. However, whether there synergistic effect between diet and 1-BP remains unclear. this study, adult C57BL/6 mice were fed either chow or 18 weeks prior 12-week treatment. Subsequent neurobehavioral neuropathological examinations conducted assess parkinsonian pathology. results demonstrated produced obvious abnormalities dopaminergic degeneration nigral region mice. Importantly, further exacerbated impact motor cognitive Mechanistic investigation revealed mitochondrial damage mtDNA release induced by activate NLRP3 cGAS-STING pathway- mediated neuroinflammatory response, ultimately lead necroptosis neurons. summary, our study unveils potential link chronic PD-like pathology no-motor defects experimental animals, long-term can promote neurotoxicity, which underscores pivotal role environmental factors

Язык: Английский

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Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

Pharmaceutics, Год журнала: 2024, Номер 16(6), С. 708 - 708

Опубликована: Май 24, 2024

Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable characterized by the gradual loss neurons, culminating in decline cognitive and/or motor functions. Alzheimer’s disease (AD) Parkinson’s (PD) most common NDs represent an enormous burden both terms human suffering economic cost. The available therapies for AD PD only provide symptomatic palliative relief limited period unable to modify diseases’ progression. Over last decades, research efforts have been focused on developing new pharmacological treatments these NDs. However, date, no breakthrough treatment has discovered. Hence, development disease-modifying drugs able halt or reverse progression remains unmet clinical need. This review summarizes major hallmarks treatment. It also sheds light potential directions that can be pursued develop new, treat PD, describing as representative examples some advances drug candidates targeting oxidative stress adenosine A2A receptors.

Язык: Английский

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CXCR3 inhibition ameliorates mitochondrial function to restrict oxidative damage via NCOA4-mediated ferritinophagy and improves the gut microbiota in mice

Free Radical Biology and Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Uncovering Potential Biomarkers and Constructing a Prediction Model Associated with Iron Metabolism in Parkinson’s Disease

Neuropsychiatric Disease and Treatment, Год журнала: 2025, Номер Volume 21, С. 437 - 449

Опубликована: Фев. 1, 2025

Parkinson's disease (PD) is a common neurodegenerative disorder. Iron metabolism abnormalities have been reported in PD patients and may contribute to pathogenesis. Our study aimed explore key genes associated with iron patients. Three datasets metabolism-related (IMRGs) were collected from the public database, merged into combined dataset. PD-related differentially expressed (DEGs) obtained intersected IMRGs acquire DEGs (IMRDEGs). Subsequently, IMRDEGs subjected functional enrichment ROC analyses. Finally, identified, followed by construction evaluation of risk score model, drug prediction, RT-qPCR analysis. A total 24 obtained. The AUC values ranged 0.599 0.781. After logistic regression SVM analyses, 10 model. value model was 0.953, demonstrating good diagnostic value. calibration curve decision analysis showed that has predictive performance clinical benefit for Additionally, 49 drugs predicted. identified as potential biomarkers, constructed patients, exhibiting diagnostic. This provide biomarkers promoting an understanding pathogenesis PD.

Язык: Английский

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Lactoferrin as a Candidate Multifunctional Therapeutic in Synucleinopathies

Brain Sciences, Год журнала: 2025, Номер 15(4), С. 380 - 380

Опубликована: Апрель 6, 2025

Lactoferrin (Lf) is a multifunctional glycoprotein with well-established antimicrobial, anti-inflammatory, and iron-binding properties. Emerging evidence suggests that Lf also plays neuroprotective role, particularly in neurodegenerative disorders characterized by protein aggregation, such as Parkinson’s disease (PD). Alpha-synuclein (aSyn) aggregation pathological hallmark of PD other synucleinopathies, contributing to neuronal dysfunction progression. Recent studies indicate may interfere aSyn iron chelation, modulation oxidative stress neuroinflammation. Additionally, Lf’s ability cross the blood-brain barrier its potential impact on gut-brain axis highlight promise therapeutic agent. This review explores mechanisms action disease-modifying therapy, innovative delivery strategies could enhance clinical applicability. By addressing dimensions we propose compelling candidate for future research development diseases.

Язык: Английский

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Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

Опубликована: Апрель 5, 2024

Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable characterized by the gradual loss neurons, culminating in decline cognitive and/or motor functions. Alzheimer’s disease (AD) Parkinson’s (PD) most common NDs represent an enormous burden both terms human suffering economic cost. The available therapies for AD PD only provide symptomatic palliative relief limited period unable to modify diseases’ progression. Over last decades, research efforts have been focused on developing new pharmacological treatments these NDs. However, date, no breakthrough treatment has discovered. Hence, development disease-modifying drugs able halt or reverse progression remains unmet clinical need. This review summarizes major hallmarks treatment. It also sheds light potential directions that can be pursued develop new, treat PD, thereby decreasing social burdens linked

Язык: Английский

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Iron chelators as mitophagy agents: Potential and limitations

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 179, С. 117407 - 117407

Опубликована: Сен. 12, 2024

Язык: Английский

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