Role of iron in brain development, aging, and neurodegenerative diseases

Annals of Medicine, Год журнала: 2025, Номер 57(1)

Опубликована: Март 4, 2025

It is now understood that iron crosses the blood-brain barrier via a complex metabolic regulatory network and participates in diverse critical biological processes within central nervous system, including oxygen transport, energy metabolism, synthesis catabolism of myelin neurotransmitters. During brain development, distributed throughout brain, playing pivotal role key such as neuronal myelination, neurotransmitter synthesis. In physiological aging, can selectively accumulate specific regions, impacting cognitive function leading to intracellular redox imbalance, mitochondrial dysfunction, lipid peroxidation, thereby accelerating aging associated pathologies. Furthermore, accumulation may be primary contributor neurodegenerative diseases Alzheimer's Parkinson's diseases. Comprehending diseases, utilizing iron-sensitive Magnetic Resonance Imaging (MRI) technology for timely detection or prediction abnormal neurological states, implementing appropriate interventions instrumental preserving normal system function.

Язык: Английский

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Novel Approaches Targeting in α-Synuclein for Parkinson's Disease: Current Progress and Future Directions for the Disease-Modifying Therapies

Brain Disorders, Год журнала: 2024, Номер unknown, С. 100163 - 100163

Опубликована: Сен. 1, 2024

Язык: Английский

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Parkinson’s Disease: Cells Succumbing to Lifelong Dopamine-Related Oxidative Stress and Other Bioenergetic Challenges

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(4), С. 2009 - 2009

Опубликована: Фев. 7, 2024

The core pathological event in Parkinson’s disease (PD) is the specific dying of dopamine (DA) neurons substantia nigra pars compacta (SNc). reasons why SNc DA are especially vulnerable and idiopathic PD has only been found humans still puzzling. two main underlying factors neuron vulnerability appear related to high production, namely (i) toxic effects cytoplasmic metabolism (ii) continuous cytosolic Ca2+ oscillations absence Ca2+-buffer protein calbindin. Both cause oxidative stress by producing highly reactive quinones increasing intra-mitochondrial concentrations, respectively. High expression human cell bodies suggested abundant presence DA-derived pigment neuromelanin, which not such abundance other species associated with toxicity at higher levels. created their production system, despite fact that SN does use unusually amounts energy, explains sensitive various genetic environmental create mitochondrial damage thereby promote PD. Aging increases multiple risk for PD, and, a large extent, accelerated aging. To prevent neurodegeneration, possible approaches discussed here (1) reducing accumulation, (2) blocking oscillations, (3) providing bioenergetic support.

Язык: Английский

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Toxic interactions between dopamine, α-synuclein, monoamine oxidase, and genes in mitochondria of Parkinson’s disease

Journal of Neural Transmission, Год журнала: 2024, Номер 131(6), С. 639 - 661

Опубликована: Янв. 9, 2024

Язык: Английский

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Virus-induced brain pathology and the neuroinflammation-inflammation continuum: the neurochemists view

Journal of Neural Transmission, Год журнала: 2024, Номер unknown

Опубликована: Янв. 23, 2024

Abstract Fascinatingly, an abundance of recent studies has subscribed to the importance cytotoxic immune mechanisms that appear increase risk/trigger for many progressive neurodegenerative disorders, including Parkinson’s disease (PD), Alzheimer’s (AD), amyotrophic lateral sclerosis, and multiple sclerosis. Events associated with neuroinflammatory cascades, such as ageing, immunologic dysfunction, eventually disruption blood–brain barrier “cytokine storm”, be orchestrated mainly through activation microglial cells communication neurons. The inflammatory processes prompt cellular protein dyshomeostasis. share a common feature marked by characteristic pathological hallmarks abnormal neuronal accumulation. These Lewy bodies contain misfolded α-synuclein aggregates in PD or case AD, they are Aβ deposits tau-containing neurofibrillary tangles. Subsequently, these further elicit neurotoxic events which contribute onset neurodegeneration its progression aggravation neuroinflammation. However, there is caveat exclusively linking neuroinflammation neurodegeneration, since it’s highly unlikely dysregulation only factor contributes manifestation disorders. It unquestionably complex interaction other factors genetics, age, environment. This endorses “multiple hit hypothesis”. Consequently, if host genetic susceptibility coupled age-related weakened system, this makes them more susceptible virus/bacteria-related infection. may trigger chronic leading dyshomeostasis accumulation, finally, lead destruction. Here, we differentiate “neuroinflammation” “inflammation” regard involvement barrier, seems intact but defect inflammation. There neuroinflammation-inflammation continuum virus-induced brain affection. Therefore, propose staging process, might developed adding blood- CSF parameters, their stage-dependent composition severeness grade. If so, suitable optimise therapeutic strategies fight beginning avoid inflammation at all.

Язык: Английский

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Crosstalk between neuroinflammation and ferroptosis: Implications for Parkinson’s disease progression

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 13, 2025

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and aggregation α-synuclein. Neuroinflammation triggered activation microglia astrocytes, which release pro-inflammatory factors that exacerbate neuronal damage. This inflammatory state also disrupts iron homeostasis, leading to occurrence ferroptosis. Ferroptosis lipid peroxidation cell membranes overload. Abnormal accumulation in brain increases oxidative stress peroxidation, further aggravating neuroinflammation damage neurons. Natural products have garnered attention for their antioxidant, anti-inflammatory, neuroprotective properties, with many plant extracts showing promising therapeutic potential PD research. study investigates roles various natural regulating The results suggest significant modulating interaction between ferroptosis, making them treatments PD. Future research should validate safety efficacy these compounds clinical applications develop novel strategies

Язык: Английский

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Oxidation of dopamine and related catechols in dopaminergic brain regions in Parkinson’s disease and during ageing in non-Parkinsonian subjects

Journal of Neural Transmission, Год журнала: 2024, Номер 131(3), С. 213 - 228

Опубликована: Янв. 18, 2024

Язык: Английский

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Role of aptamer technology in extracellular vesicle biology and therapeutic applications

Nanoscale, Год журнала: 2024, Номер 16(24), С. 11457 - 11479

Опубликована: Янв. 1, 2024

Extracellular vesicles (EVs) are cell-derived nanosized membrane-bound that important intercellular signalling regulators in local cell-to-cell and distant cell-to-tissue communication. Their inherent capacity to transverse cell membranes transfer complex bioactive cargo reflective of their source, as well ability be modified through various engineering modification strategies, have attracted significant therapeutic interest. Molecular bioengineering strategies providing a new frontier for EV-based therapy, including novel mRNA vaccines, antigen cross-presentation immunotherapy, organ delivery repair, cancer immune surveillance targeted therapeutics. The revolution EVs, diversity biocarriers potential contribute communication, is understood appreciated but ultimately dependent on the development methods techniques isolation, characterization enhanced targeting. As single-stranded oligonucleotides, aptamers, also known chemical antibodies, offer biological, chemical, economic, advantages terms size, selectivity, versatility, multifunctional programming. integration into field EVs has been contributing detection, analysis pipelines associated with nano-meets-molecular biology, thus translating use diagnostic utility.

Язык: Английский

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Catecholamines and Parkinson’s disease: tyrosine hydroxylase (TH) over tetrahydrobiopterin (BH4) and GTP cyclohydrolase I (GCH1) to cytokines, neuromelanin, and gene therapy: a historical overview

Journal of Neural Transmission, Год журнала: 2023, Номер 131(6), С. 617 - 630

Опубликована: Авг. 28, 2023

Язык: Английский

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Reanalysis of DIA Data Demonstrates the Capabilities of MS/MS-Free Proteomics to Reveal New Biological Insights in Disease-Related Samples

Journal of the American Society for Mass Spectrometry, Год журнала: 2024, Номер 35(8), С. 1775 - 1785

Опубликована: Июнь 28, 2024

Data-independent acquisition (DIA) at the shortened data time is becoming a method of choice for quantitative proteomic applications requiring high throughput analysis large cohorts samples. With advent combination resolution mass spectrometry with an asymmetric track lossless analyzer, these DIA capabilities were further extended recent demonstration analyses speed up to hundreds samples per day. In particular, brain related multiple system atrophy disease acquired using 7 and 28 min chromatography gradients (Guzman et al.,

Язык: Английский

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