The Irony of Iron: The Element with Diverse Influence on Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4269 - 4269

Published: April 12, 2024

Iron accumulation in the brain is a common feature of many neurodegenerative diseases. Its involvement spans across main proteinopathies involving tau, amyloid-beta, alpha-synuclein, and TDP-43. Accumulating evidence supports contribution iron disease pathologies, but delineation its pathogenic role yet challenged by complex multiple neurotoxicity mechanisms supporting reciprocal influence between protein pathology. Here, we review major proteinopathy-specific observations four distinct hypotheses: (1) deposition consequence pathology; (2) promotes (3) protects from or hinders (4) pathology contribute parallelly to pathogenesis. an essential element for physiological function, requiring fine balance levels. Understanding disease-related at more intricate systemic level critical advancements chelation therapies.

Language: Английский

---

The role and impact of abnormal vitamin levels in autism spectrum disorders

Food & Function, Journal Year: 2024, Volume and Issue: 15(3), P. 1099 - 1115

Published: Jan. 1, 2024

This is a review of several vitamins (A, B, C, D, E, and K) that have been closely linked to the development autism, exploring their mechanisms action significance in prevention, mitigation, treatment autism.

Language: Английский

---

Cerebral iron accumulation in multiple sclerosis: Pathophysiology and therapeutic implications

Autoimmunity Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 103741 - 103741

Published: Jan. 1, 2025

Language: Английский

---

Causal associations between iron levels in subcortical brain regions and psychiatric disorders: a Mendelian randomization study

Translational Psychiatry, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 22, 2025

Despite observational studies linking brain iron levels to psychiatric disorders, the exact causal relationship remains poorly understood. This study aims examine between in specific subcortical regions and risk of disorders. Utilizing two-sample Mendelian randomization (MR) analysis, this investigates associations level changes 16 nuclei eight major including schizophrenia (SCZ), depressive disorder (MDD), autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder, bipolar anxiety obsessive-compulsive insomnia. The genetic instrumental variables linked were derived from genome-wide association data UK Biobank Brain Imaging Psychiatric Genomics Consortium. Bidirectional estimation was primarily obtained using inverse variance weighting (IVW) method. Iron left substantia nigra showed a negative with MDD (ORIVW = 0.94, 95% CI 0.91–0.97, p < 0.001) trends SCZ 0.90, 0.82–0.98, 0.020). Conversely, putamen positively associated ASD 1.11, 1.04–1.19, 0.002). Additionally, several bidirectional observed for Lower may increase MDD, potentially SCZ, indicating potential shared pathogenic mechanism. Higher lead development ASD. indicate importance underlying biomechanical interactions regulation these

Language: Английский

---

Emerging Ferroptosis Involvement in Amyotrophic Lateral Sclerosis Pathogenesis: Neuroprotective Activity of Polyphenols

Molecules, Journal Year: 2025, Volume and Issue: 30(6), P. 1211 - 1211

Published: March 8, 2025

Neurodegenerative diseases are a group of that share common features, such as the generation misfolded protein deposits and increased oxidative stress. Among them, amyotrophic lateral sclerosis (ALS), whose pathogenesis is still not entirely clear, complex neurodegenerative disease linked both to gene mutations affecting different proteins, superoxide dismutase 1, Tar DNA binding 43, Chromosome 9 open frame 72, Fused in Sarcoma, altered iron homeostasis, mitochondrial dysfunction, stress, impaired glutamate metabolism. The purpose this review highlight molecular targets ALS ferroptosis. Indeed, many pathways implicated hallmarks ferroptosis, recently discovered type iron-dependent programmed cell death characterized by reactive oxygen species (ROS) lipid peroxidation. Iron accumulation results dysfunction levels ROS, peroxidation, ferroptosis triggers; addition, inhibition Xc− system reduced cystine accumulation, leading excitotoxicity GPx4 synthesis. These potential involvement ALS, providing new biochemical could be exploited treatment using polyphenols.

Language: Английский

---

Combined transcriptomic and proteomic analyses reveal relevant myelin features in mice with ischemic stroke

Functional & Integrative Genomics, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 14, 2025

Ischemic stroke (IS), a leading cause of global disability and mortality, is characterized by white matter damage demyelination. Despite advances, the molecular mechanisms driving post-IS myelin pathology remain poorly understood, limiting therapeutic development. This study investigates key myelin-related genes (MRGs) their regulatory networks to identify novel targets. A transient middle cerebral artery occlusion (MCAO) model was established in C57BL/6 mice, with brain tissues collected at four timepoints (Sham0D, MCAO0D, MCAO7D, MCAO14D). Transcriptomic proteomic sequencing were performed, followed soft clustering (Mfuzz), functional enrichment (GO/KEGG), ROC analysis MRGs. Competing endogenous RNA (ceRNA) constructed, drug prediction conducted using Comparative Toxicogenomics Database (CTD) docking. Expression validation performed via qRT-PCR Western blot. Integrated multi-omics identified Wasf3 Slc25a5 as MRGs, enriched mitochondrial respiration, calcium metabolism, cytoskeletal regulation. The AUC values one-to-one scores all greater than 0.7, suggesting that able effectively discriminate between samples from different time points. ceRNA network revealed critical interactions, including Wasf3-mmu-miR-423-5p-H19 axis, linking apoptosis dysfunction. Drug highlighted valproic acid (VPA) high-affinity binder for both (binding energies: − 4.2 4.7 kcal/mol), its potential candidate IS. Experimental confirmed significant downregulation mRNA (p < 0.01) protein = 0.069) post-IS, while showed no changes, potentially due sample size limitations. establishes pivotal regulators proposes VPA promising enhance remyelination. findings underscore utility approaches bridging clinical translation, offering new strategies IS diagnosis treatment.

Language: Английский

---

Iron Metabolism and the Role of Iron Therapy in Pediatric Restless Leg Syndrome

Sleep Medicine Clinics, Journal Year: 2025, Volume and Issue: 20(2), P. 231 - 238

Published: March 19, 2025

Language: Английский

---

Absence of Astrocytic Ceruloplasmin Reverses the Senescence Process with Aging of Learning and Memory Abilities

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103611 - 103611

Published: March 1, 2025

Ceruloplasmin (CP) is a multi-copper ferroxidase mainly synthesized by liver, secreted into the peripheral blood, playing critical role in regulating iron homeostasis. In central nervous system (CNS), CP expressed astrocytes plays an important transportation of from blood across blood-brain barrier (BBB) brain. Our previous study showed that conditional knockout astrocytic with Cre-LoxP (CpGfapcKO) not only improved learning and memory abilities elderly mice, but also impaired young mice. order to further investigate effects on aging, we constructed mice model tamoxifen-induced astrocyte specific CP, induced at 12 months old, observed mouse 18 old. We were delighted found ablation tamoxifen old could similarly enhance learning, recognition 18-month-old Iron deposition hippocampus associated aging was mitigated, leading reduction oxidative stress. The MAPK/JNK pathway exhibited attenuation, while PI3K/Akt/GSK3 enhancement. This combination expected result phosphorylation level MYC elevation nuclear translocation MYC, which might then contribute reduced cellular senescence. Additionally, ROS/MAPK/Erk ROS/MAPK/p38 pathways-dependent cell apoptosis diminished. hallmarks Alzheimer's Disease (AD) all significantly reduced. Ultimately, alleviated senescence along AD-related markers, coincided improvement memory, abilities. These findings elucidated brain metabolism, offering novel target strategy for prevention treatment neurodegenerative diseases, such as AD aging.

Language: Английский

---

Sulfonamide-functionalized Schiff’s base as a novel fluorescent probe for selective detection of L-tryptophan in real and biological samples

Microchemical Journal, Journal Year: 2025, Volume and Issue: unknown, P. 113754 - 113754

Published: April 1, 2025

Language: Английский

---

Electromagnetic fields regulate iron metabolism: From mechanisms to applications

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Electromagnetic fields (EMFs), as a form of physical therapy, have been widely applied in biomedicine. Iron, the most abundant trace metal living organisms, plays critical role various physiological processes, and imbalances its metabolism are closely associated with development progression numerous diseases. Numerous studies demonstrated that EMF exposureinduces significant changes both systemic cellular iron metabolism. This review aims to summarize evidence potential biophysical mechanisms underlying EMFs regulating metabolism, thereby enhancing understanding their biological expanding applications biomedical fields. In this review, we synthesized research findings proposed hypothesis regulate involve special electromagnetic properties iron-containing proteins iron-enriched tissues, well modulation membrane structure function, ion channels, generation activity Reactive Oxygen Species (ROS). Then, summarizes latest advances effects on safety, impact immunoregulation, cardiovascular diseases, neurological orthopedic diabetes, liver injury, cancer.

Language: Английский

---