The Underestimated Role of Iron in Frontotemporal Dementia: A Narrative Review DOI Open Access

Sara Ferretti,

Isabella Zanella

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 12987 - 12987

Опубликована: Дек. 3, 2024

The term frontotemporal dementia (FTD) comprises a group of neurodegenerative disorders characterized by the progressive degeneration frontal and temporal lobes brain with language impairment changes in cognitive, behavioral executive functions, some cases motor manifestations. A high proportion FTD are due to genetic mutations inherited an autosomal-dominant manner variable penetrance depending on implicated gene. Iron is crucial microelement that involved several cellular essential functions whole body plays additional specialized roles central nervous system (CNS) mainly through its redox-cycling properties. Such feature may be harmful under aerobic conditions, since it lead generation highly reactive hydroxyl radicals. Dysfunctions iron homeostasis CNS indeed disorders, although still challenging determine whether dyshomeostasis this but metal direct cause neurodegeneration, contributor factor or simply consequence other mechanisms. Unlike many evidence dysfunction scarce; nonetheless, recent literature intriguingly suggests possible involvement. present review aims summarize what currently known about contribution based clinical, imaging, histological, biochemical molecular studies, further suggesting new perspectives offering insights for future investigations underexplored field research.

Язык: Английский

Cell death pathways: molecular mechanisms and therapeutic targets for cancer DOI Creative Commons
Shaohui Wang, Sa Guo, Jing Guo

и другие.

MedComm, Год журнала: 2024, Номер 5(9)

Опубликована: Сен. 1, 2024

Abstract Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell can provide novel therapeutic strategies battling cancer. This review explores several key mechanisms apoptosis, necroptosis, autophagic death, ferroptosis, pyroptosis. The research gap addressed involves a thorough analysis how these be precisely targeted therapy, considering tumor heterogeneity adaptation. It delves into genetic epigenetic factors signaling cascades like phosphatidylinositol 3‐kinase/protein kinase B/mammalian target rapamycin (PI3K/AKT/mTOR) mitogen‐activated protein kinase/extracellular signal‐regulated (MAPK/ERK) pathways, which are critical death. Additionally, interaction microenvironment with cells, particularly influence hypoxia, nutrient deprivation, immune cellular interactions, explored. Emphasizing strategies, this highlights emerging modulators inducers such as B lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL), chloroquine, innovative approaches to induce ferroptosis provides insights therapy's future direction, focusing on multifaceted circumvent drug resistance. examination evolving underlines considerable clinical potential continuous necessity in‐depth exploration within scientific domain.

Язык: Английский

Процитировано

12
Major heme proteins hemoglobin and myoglobin with respect to their roles in oxidative stress – a brief review DOI Creative Commons

Rajarshi Sil,

Abhay Sankar Chakraborti

Frontiers in Chemistry, Год журнала: 2025, Номер 13

Опубликована: Фев. 25, 2025

Oxidative stress is considered as the root-cause of different pathological conditions. Transition metals, because their redox-active states, are capable free radical generation contributing oxidative stress. Hemoglobin and myoglobin two major heme proteins, involved in oxygen transport storage, respectively. Heme prosthetic group proteins a good reservoir iron, most abundant transition metal human body. Although iron tightly bound pocket these it liberated under specific circumstances yielding ferrous iron. This active can react with H2O2, secondary metabolite, forming hydroxyl via Fenton reaction. Hydroxyl harmful among all reactive species. It causes by damaging lipid membranes, nucleic acids, activating inflammatory pathways altering membrane channels, resulting disease In this review, we have discussed how heme-irons hemoglobin promote pathophysiological conditions including metabolic syndrome, diabetes, cardiovascular, neurodegenerative renal diseases. Understanding association to may be important for knowing complications well therapeutic management

Язык: Английский

Процитировано

0
Epigenetic regulation of iron metabolism and ferroptosis in Parkinson’s disease: Identifying novel epigenetic targets DOI

Xiaodie Gao,

Jun Ding, Junxia Xie

и другие.

Acta Pharmacologica Sinica, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

Язык: Английский

Процитировано

0
Integration of Transcriptomic and Single-Cell Data to Uncover Senescence- and Ferroptosis-Associated Biomarkers in Sepsis DOI Creative Commons
Xiangqian Zhang, Yiran Zhou, Hang Li

и другие.

Biomedicines, Год журнала: 2025, Номер 13(4), С. 942 - 942

Опубликована: Апрель 11, 2025

Background: Sepsis is a life-threatening condition characterized by organ dysfunction due to an imbalanced immune response infection, with high mortality. Ferroptosis, iron-dependent cell death process, and cellular senescence, which exacerbates inflammation, have recently been implicated in sepsis pathophysiology. Methods: Weighted gene co-expression network analysis (WGCNA) was used identify ferroptosis- senescence-related modules sepsis. Differentially expressed genes (DEGs) were analyzed using public datasets (GSE57065, GSE65682, GSE26378). Receiver operating characteristic (ROC) performed evaluate their diagnostic potential, while single-cell RNA sequencing (scRNA-seq) assess immune-cell-specific expression. Molecular docking conducted predict drug interactions key proteins. Results: Five (CD82, MAPK14, NEDD4, TXN, WIPI1) significantly upregulated patients highly correlated infiltration. MAPK14 TXN exhibited strong potential (AUC = 0.983, 0.978). suggested therapeutic diclofenac, flurbiprofen, N-acetyl-L-cysteine. Conclusions: This study highlights ferroptosis senescence as critical mechanisms identifies promising biomarkers for diagnosis targeted therapy. Future studies should focus on clinical validation precision medicine applications.

Язык: Английский

Процитировано

0
Neuroferritinopathy comprehensive review DOI Open Access
Anmol Sharma, Jitender Kumar Sharma

IP Indian Journal of Neurosciences, Год журнала: 2024, Номер 10(4), С. 182 - 189

Опубликована: Ноя. 15, 2024

Neuroferritinopathy is a rare, autosomal dominant neurodegenerative disorder characterized by the accumulation of iron in brain due to mutations ferritin light chain gene (FTL). This article explores incidence, prevalence, pathogenesis, types, and treatment options for neuroferritinopathy, drawing on current scientific literature provide comprehensive overview. clinically presents mid-adulthood, most frequently between third fifth decade life. Onset: Symptoms are often gradual, though patients may develop dystonia, chorea, parkinsonism, cognitive dysfunction.

Язык: Английский

Процитировано

0
Neurodegeneration with iron accumulation in the brain, peculiarities of course and approach to treatment DOI Open Access
T.A. DOVBONOS, V.O. Svystilnyk, Victoria Y. Krylova

и другие.

INTERNATIONAL NEUROLOGICAL JOURNAL, Год журнала: 2024, Номер 20(7), С. 375 - 381

Опубликована: Дек. 3, 2024

Neurodegenerations with brain iron accumulation (NBIA) constitute a group of genetically determined and clinically heterogeneous forms progressive neurological pathology associated the in basal ganglia other structures brain, which, turn, causes their dysfunction. Both childhood adulthood onset disease is possible. Objective: to draw attention doctors importance timely diagnosis neurodegenerative diseases, which are manifested by movement disorders abnormal various brain. Movement disorders, mostly combination parkinsonism, dystonia, pyramidal insufficiency ataxia, dominant clinical picture NBIA. Areas deposition detected on magnetic resonance imaging as bilateral hypodense zones, center hyperdense foci many cases, probably due gliosis, mainly area globus pallidus (eye-of-the-tiger sign). Typical neuroimaging signs help make preliminary NBIA high probability, presence sometimes even before appearance manifestations disease, reducing costs time for additional research. The paper describes case protein mitochondrial membrane, also highlights latest data manifestations, modern management this pathology. possibility therapy have been demonstrated. Genetic examination remains crucial verification hereditary degenerative determination its form. analysis literature results own observations confirm given main directions available symptomatic treatment, well approaches pathogenetic therapy, still require further trials. observation problem reflect expediency searching characteristic patterns patients motor (extrapyramidal, pyramidal, coordination) means molecular genetic

Язык: Английский

Процитировано

0
The Underestimated Role of Iron in Frontotemporal Dementia: A Narrative Review DOI Open Access

Sara Ferretti,

Isabella Zanella

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 12987 - 12987

Опубликована: Дек. 3, 2024

The term frontotemporal dementia (FTD) comprises a group of neurodegenerative disorders characterized by the progressive degeneration frontal and temporal lobes brain with language impairment changes in cognitive, behavioral executive functions, some cases motor manifestations. A high proportion FTD are due to genetic mutations inherited an autosomal-dominant manner variable penetrance depending on implicated gene. Iron is crucial microelement that involved several cellular essential functions whole body plays additional specialized roles central nervous system (CNS) mainly through its redox-cycling properties. Such feature may be harmful under aerobic conditions, since it lead generation highly reactive hydroxyl radicals. Dysfunctions iron homeostasis CNS indeed disorders, although still challenging determine whether dyshomeostasis this but metal direct cause neurodegeneration, contributor factor or simply consequence other mechanisms. Unlike many evidence dysfunction scarce; nonetheless, recent literature intriguingly suggests possible involvement. present review aims summarize what currently known about contribution based clinical, imaging, histological, biochemical molecular studies, further suggesting new perspectives offering insights for future investigations underexplored field research.

Язык: Английский

Процитировано

0