Targeting Ferroptosis in Parkinson’s: Repurposing Diabetes Drugs as a Promising Treatment

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1516 - 1516

Опубликована: Фев. 11, 2025

This review explores the promising potential of repurposing type 2 diabetes (T2D) medications for treatment Parkinson's disease (PD), highlighting shared pathophysiological mechanisms between these two age-related conditions, such as oxidative stress, mitochondrial dysfunction, and ferroptosis. The overlap suggests that existing drugs could target common pathways involved in both conditions. Specifically, discusses how T2D medications, including metformin (Met), peroxisome-proliferator-activated receptor gamma (PPAR-γ) agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, incretins, dipeptidyl-peptidase 4 (DPP-4) can improve function, reduce neuroinflammation potentially inhibit connection ferroptosis treatments, medication, are only beginning to be explored. limited data attributed also complexity fact specific role pathogenesis has not been a primary focus until recent. Despite preclinical evidence, clinical findings mixed, underscoring need further research elucidate drugs' roles neurodegeneration. Repurposing have well-established safety profiles significantly time cost associated with drug development offer more comprehensive approach managing compared treatments targeting single mechanism.

Язык: Английский

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Deciphering the Genetic Architecture of Parkinsons Disease in India

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 21, 2025

Abstract The genomic landscape of the Indian population, particularly for age-related disorders like Parkinson’s disease (PD) remains underrepresented in global research. Genetic variability PD has been studied predominantly European populations, offering limited insights into its role within population. To address this gap, we conducted first pan-India survey involving 4,806 cases and 6,364 controls, complemented by a meta-analysis integrating summary statistics from multi-ancestry (N=611,485). We further leveraged RNA-sequencing data lymphoblastoid cell lines 731 individuals 1000 Genomes project to evaluate expression key loci across populations. Our findings reveal higher genetic burden population compared Europeans, accounting ∼30% previously unexplained heritability. Thirteen genome-wide significant were identified, including two novel loci, with an additional three uncovered through meta-analysis. Polygenic risk score analysis showed moderate transferability results highlight importance immune function, lipid metabolism SNCA aggregation pathogenesis, gene emphasizing population-specific differences. also established South Asia’s largest biobank, providing foundation patient-centric approaches research treatment India.

Язык: Английский

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Insulin signaling disruption exacerbates memory impairment and seizure susceptibility in an epilepsy model with Alzheimer’s disease-like pathology

Journal of Neural Transmission, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Язык: Английский

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Interplay between endogenous hormones and immune systems in human metapneumovirus pathogenesis and management

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 19, 2025

The present review explores the role of endogenous hormones, such as cortisol, melatonin, thyroid sex and insulin, in modulation immune response to a human metapneumovirus (hMPV) infection. hMPV is respiratory pathogen responsible for severe infections, particularly vulnerable populations like children elderly. virus triggers inflammatory responses through various molecular processes, including cytokine production signaling pathways. Notably, these processes can be influenced by endocrine factors, hormones. Cortisol, hypothalamic-pituitary-adrenal (HPA) axis activation, modulates inflammation but may contribute immunosuppression. Melatonin inhibits NLRP3 inflammasome, reducing lung inflammation. Thyroid hormones regulate via nuclear factor kappa B (NF-κB) JAK/STAT pathways, while hypothyroidism alter infection severity. Sex estrogens, enhance antiviral immunity, whereas androgens have variable effects on modulation. Insulin influences NF-κB suppression, with insulin resistance potentially worsening viral pathogenesis. Therapeutic implications suggest that modulating hormonal pathways could aid management. Strategies hormone therapy, glucocorticoid regulation, nanoparticle-based drug delivery are potential routes intervention. aim understand complex interplay between system during an describing mechanisms associated processes.

Язык: Английский

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Incretin-based therapeutics for the treatment of neurodegenerative diseases

Nature Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Апрель 10, 2025

Язык: Английский

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The impact of diabetes mellitus on the development of psychiatric and neurological disorders

Brain Disorders, Год журнала: 2024, Номер 14, С. 100135 - 100135

Опубликована: Апрель 17, 2024

Diabetes mellitus (DM) is a chronic condition resulting from insulin deficiency or systemic resistance. In this disorder, either the pancreatic β-cells are unable to produce enough insulin, secreted ineffective overcome peripheral central Over time, glucose metabolism becomes dysregulated, in overt DM characterized by hyperglycemia and inflammation. This research review explores connections potential correlations between various psychiatric neurological disorders, including major depressive disorder (MDD), Parkinson's disease (PD), Alzheimer's (AD). While no claims of direct causation can be made, does show significant associations with MDD, PD, AD. Each these conditions shows some overlap among risk factors, biological pathways, mechanisms, therapeutic approaches DM. Interestingly, depending on factor, influence progression PD AD, vice versa. pathophysiological pathways molecular events associated disorders allows for further investigation into establishing each conditions.

Язык: Английский

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Intranasal insulin treatment ameliorates spatial memory, muscular strength, and frailty deficits in 5xFAD mice

Physiology & Behavior, Год журнала: 2024, Номер 281, С. 114583 - 114583

Опубликована: Май 14, 2024

Язык: Английский

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Insulin Resistance Is a Modifying Factor for Parkinson's Disease

Movement Disorders, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 5, 2024

Abstract Background Parkinson's disease (PD) is the second most common, and fastest‐growing neurodegenerative disorder with unclear etiology in cases. Therefore, identification of non‐genetic risk factors for PD pathology crucial to develop effective preventative or therapeutic strategies. An increasing number evidence suggests that central insulin resistance might have an essential role pathology. Nevertheless, it not clear whether arises from external factors/lifestyle, comorbidities such as type 2 diabetes can occur a patient's brain independently peripheral resistance. Objective We aimed investigate its GBA1 mutation‐associated pathogenesis phenotype severity. Methods Midbrain organoids, generated induced pluripotent stem cells (iPSCs) patients carrying ‐N370S heterozygous mutation (GBA‐PD) healthy donors, were exposed different concentrations modify signaling function. Transcriptomics analysis was performed explore gene expression patterns GBA‐PD find potential target GBA‐PD‐associated rescue. Results The pathway genes show dysregulation GBA‐PD. Particularly, we highlight knockdown FOXO1 mitigates loss dopaminergic neurons cellular death Additionally, our findings suggest promising anti‐diabetic drug Pioglitazone decreasing neuron associated Conclusion Local dysfunction plays substantial pathogenesis, exacerbating death. © 2024 Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf International Parkinson Disorder Society.

Язык: Английский

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Heavy metals in the diet: unraveling the molecular pathways linked to neurodegenerative disease risk

Food and Agricultural Immunology, Год журнала: 2024, Номер 35(1)

Опубликована: Дек. 3, 2024

Neurodegenerative diseases (NDDs) affect millions of lives worldwide. They constitute a group neurological disorders with shared common features, including impaired cognition, behavior, memory, and motor functions. These conditions arise due to the gradual degeneration neurons within nervous system. Even though, each pathology presents diverse etiologies develops in different brain sites, they may share cellular molecular mechanisms, such as inflammation, protein aggregation, DNA RNA defects. Heavy metal contamination is global public health concern, given that anthropogenic activities like paint manufacturing, mining, oil refining contribute substantially heavy pollution. Consequently, studies have investigated its potential etiological factors neurodegenerative diseases. This review examines impact dietary exposure metals, specifically mercury, cadmium, lead, chromium, arsenic, zinc, on development progression Evidence from range indicates these metals play significant role advancing by disrupting essential functions, induction oxidative stress impairments mitochondrial function. findings underscore need for further research elucidate toxicological mechanisms develop preventive strategies, chelation therapies environmental remediation. Addressing risks especially critical protect neurocognitive health, particularly aging populations.

Язык: Английский

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MODELING OF PARKINSON'S DISEASE BY INTRASTRIATAL ADMINISTRATION OF STREPTOZOTOCIN

Neuropharmacology, Год журнала: 2024, Номер 265, С. 110246 - 110246

Опубликована: Дек. 4, 2024

Язык: Английский

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