Iron and Targeted Iron Therapy in Alzheimer’s Disease

Wang, Jian; Fu, Jiaying; Zhao, Yuanxin; Liu, Qingqing; Yan, Xiaoyu; Su, Jing

doi:10.3390/ijms242216353

Cited by 7 publications

(5 citation statements)

References 165 publications

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“…Finally, translating the growing understanding of iron-induced neuroinflammation into effective therapeutic and preventative strategies could be fruitful. This could involve exploring chelation therapy to remove excess iron from the brain [ 62 ], developing anti-inflammatory drugs targeted specifically for the brain, and investigating dietary and lifestyle modifications that can mitigate iron accumulation and neuroinflammation. While further research is clearly needed, the current evidence suggests a strong plausible connection among alcohol-related iron overload, neuroinflammation, and cognitive decline.…”

Section: Discussionmentioning

confidence: 99%

“…A recent review involving two iron chelating agents, M30 and HLA20, suggested the neuroprotective role of iron-chelating agents in animal models by reducing neurodegenerative pathology, upregulating signalling pathways that provide neuronal protection, and providing positive behavioural modification [ 37 ]. Several studies have recently proposed the utilisation of iron-chelating agents for the treatment of Alzheimer’s disease [ 62 , 64 ]. Another study used alpha-lipoic acid in transgenic mice models, which prevented tau-hyperphosphorylation and reduced oxidative stress, inflammation, and ferroptosis in neuronal cells [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

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Could Alcohol-Related Cognitive Decline Be the Result of Iron-Induced Neuroinflammation?

Wilcockson,

Roy

2024

Brain Sciences

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Excessive and prolonged alcohol use can have long-term severe neurological consequences. The mechanisms involved may be complicated; however, new evidence seems to indicate the involvement of iron accumulation and neuroinflammation. Prolonged alcohol consumption has been linked to the accumulation of iron in specific regions of the brain. Evidence suggests that excess iron in the brain can trigger microglia activation in response. This activation leads to the release of pro-inflammatory cytokines and reactive oxygen species, which can cause damage to neurons and surrounding brain tissue. Additionally, iron-induced oxidative stress and inflammation can disrupt the blood–brain barrier, allowing immune cells from the periphery to infiltrate the brain. This infiltration can lead to further neuroinflammatory responses. Inflammation in the brain subsequently disrupts neuronal networks, impairs synaptic plasticity, and accelerates neuronal cell death. Consequently, cognitive functions such as memory, attention, and decision-making are compromised. Additionally, chronic neuroinflammation can hasten the development and progression of neurodegenerative diseases, further exacerbating cognitive impairment. Therefore, alcohol could act as a trigger for iron-induced neuroinflammation and cognitive decline. Overall, the mechanisms at play here seem to strongly link alcohol with cognitive decline, with neuroinflammation resulting from alcohol-induced iron accumulation playing a pivotal role.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Could Alcohol-Related Cognitive Decline Be the Result of Iron-Induced Neuroinflammation?

Wilcockson,

Roy

2024

Brain Sciences

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“…On the other hand, clioquinol has been withdrawn from the antibiotic market due to its association with subacute myelo-optic neuropathy. Hence, clinical investigations of recently developed second-generation clioquinol are important [6,[130][131][132].…”

Section: Alzheimer's Disease Therapies That Might Target Elementsmentioning

confidence: 99%

Trace Elements in Alzheimer’s Disease and Dementia: The Current State of Knowledge

Tyczyńska,

Gędek,

Brachet

et al. 2024

JCM

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Changes in trace element concentrations are being wildly considered when it comes to neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. This study aims to present the role that trace elements play in the central nervous system. Moreover, we reviewed the mechanisms involved in their neurotoxicity. Low zinc concentrations, as well as high levels of copper, manganese, and iron, activate the signalling pathways of the inflammatory, oxidative and nitrosative stress response. Neurodegeneration occurs due to the association between metals and proteins, which is then followed by aggregate formation, mitochondrial disorder, and, ultimately, cell death. In Alzheimer’s disease, low Zn levels suppress the neurotoxicity induced by β-amyloid through the selective precipitation of aggregation intermediates. High concentrations of copper, iron and manganese cause the aggregation of intracellular α-synuclein, which results in synaptic dysfunction and axonal transport disruption. Parkinson’s disease is caused by the accumulation of Fe in the midbrain dopaminergic nucleus, and the pathogenesis of multiple sclerosis derives from Zn deficiency, leading to an imbalance between T cell functions. Aluminium disturbs the homeostasis of other metals through a rise in the production of oxygen reactive forms, which then leads to cellular death. Selenium, in association with iron, plays a distinct role in the process of ferroptosis. Outlining the influence that metals have on oxidoreduction processes is crucial to recognising the pathophysiology of neurodegenerative diseases and may provide possible new methods for both their avoidance and therapy.

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“…DFO, DFP, and DFX are Food and Drug Administration (FDA)-approved iron chelators capable of crossing the BBB [ 42 ]. Recently, it has been shown that these agents can lower iron accumulation in patients with AD [ 43 ]. DFO binds iron in a 1:1 ratio and is a hexadentate ligand [ 44 ].…”

Section: Metal Chelators For the Potential Treatment Of Admentioning

confidence: 99%

Targeting Biometals in Alzheimer’s Disease with Metal Chelating Agents Including Coumarin Derivatives

Gucký,

Hamuľaková

2024

CNS Drugs

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Numerous physiological processes happening in the human body, including cerebral development and function, require the participation of biometal ions such as iron, copper, and zinc. Their dyshomeostasis may, however, contribute to the onset of Alzheimer’s disease (AD) and potentially other neurodegenerative diseases. Chelation of biometal ions is therefore a therapeutic strategy against AD. This review provides a survey of natural and synthetic chelating agents that are or could potentially be used to target the metal hypothesis of AD. Since metal dyshomeostasis is not the only pathological aspect of AD, and the nature of this disorder is very complex and multifactiorial, the most efficient therapeutics should target as many neurotoxic factors as possible. Various coumarin derivatives match this description and apart from being able to chelate metal ions, they exhibit the capacity to inhibit cholinesterases (ChEs) and monoamine oxidase B (MAO-B) while also possessing antioxidant, anti-inflammatory, and numerous other beneficial effects. Compounds based on the coumarin scaffold therefore represent a desirable class of anti-AD therapeutics.

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Iron and Targeted Iron Therapy in Alzheimer’s Disease

Cited by 7 publications

References 165 publications

Could Alcohol-Related Cognitive Decline Be the Result of Iron-Induced Neuroinflammation?

Could Alcohol-Related Cognitive Decline Be the Result of Iron-Induced Neuroinflammation?

Trace Elements in Alzheimer’s Disease and Dementia: The Current State of Knowledge

Targeting Biometals in Alzheimer’s Disease with Metal Chelating Agents Including Coumarin Derivatives

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