Beneficial and Detrimental Roles of Heme Oxygenase-1 in the Neurovascular System

Choi, Yoon Kyung; Kim, Young-Myeong

doi:10.3390/ijms23137041

Cited by 23 publications

(33 citation statements)

References 143 publications

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“…Free Fe 3+ induces aggregation of hyperphosphorylated tau. On the other hand, Fe 2+ can reverse the aggregation [ 436 ]. Discrepancies in expression levels of iron transport-related proteins such as ferritin [ 412 , 436 ] may be due to the differences in samples utilized in the studies.…”

Section: Metal Ion Imbalance In Ad (Heme Fe Cu Zn)mentioning

confidence: 99%

“…On the other hand, Fe 2+ can reverse the aggregation [ 436 ]. Discrepancies in expression levels of iron transport-related proteins such as ferritin [ 412 , 436 ] may be due to the differences in samples utilized in the studies. Therefore, further studies involving populations from different races, sexes, genders, ages, and ethnic groups are required to elucidate iron’s role in AD pathology.…”

Section: Metal Ion Imbalance In Ad (Heme Fe Cu Zn)mentioning

confidence: 99%

“…Heme excess promotes ROS production, leading to oxidative stress, lipid peroxidation, and cell death [ 437 , 438 ]. Studies in the brains of patients with AD showed that iron overload in the inferior temporal cortex may be involved in accelerated cognitive decline [ 436 ]. Dysregulation of heme metabolism and elevated heme/iron levels are associated with a poor prognosis in AD.…”

Section: Metal Ion Imbalance In Ad (Heme Fe Cu Zn)mentioning

confidence: 99%

“…Moreover, HO-1 upregulation and post-transcriptional modifications were detected in the brains of patients with AD in a previous study. Mouse studies demonstrated that HO-1 overexpression induces tau phosphorylation and facilitates aggregation [ 436 , 442 , 443 ]. HO-1 upregulation can induce Fe 2+ excess in the cytoplasm, promote oxidative stress, and promote ferroptosis.…”

Section: Metal Ion Imbalance In Ad (Heme Fe Cu Zn)mentioning

confidence: 99%

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Recent Development in the Understanding of Molecular and Cellular Mechanisms Underlying the Etiopathogenesis of Alzheimer’s Disease

Afsar

Castro

Soladogun

et al. 2023

IJMS

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that leads to dementia and patient death. AD is characterized by intracellular neurofibrillary tangles, extracellular amyloid beta (Aβ) plaque deposition, and neurodegeneration. Diverse alterations have been associated with AD progression, including genetic mutations, neuroinflammation, blood–brain barrier (BBB) impairment, mitochondrial dysfunction, oxidative stress, and metal ion imbalance.Additionally, recent studies have shown an association between altered heme metabolism and AD. Unfortunately, decades of research and drug development have not produced any effective treatments for AD. Therefore, understanding the cellular and molecular mechanisms underlying AD pathology and identifying potential therapeutic targets are crucial for AD drug development. This review discusses the most common alterations associated with AD and promising therapeutic targets for AD drug discovery. Furthermore, it highlights the role of heme in AD development and summarizes mathematical models of AD, including a stochastic mathematical model of AD and mathematical models of the effect of Aβ on AD. We also summarize the potential treatment strategies that these models can offer in clinical trials.

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Section: Metal Ion Imbalance In Ad (Heme Fe Cu Zn)mentioning

confidence: 99%

Section: Metal Ion Imbalance In Ad (Heme Fe Cu Zn)mentioning

confidence: 99%

Section: Metal Ion Imbalance In Ad (Heme Fe Cu Zn)mentioning

confidence: 99%

Section: Metal Ion Imbalance In Ad (Heme Fe Cu Zn)mentioning

confidence: 99%

See 2 more Smart Citations

Recent Development in the Understanding of Molecular and Cellular Mechanisms Underlying the Etiopathogenesis of Alzheimer’s Disease

Afsar

Castro

Soladogun

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Nrf2 is regulated by P62, which inhibits Nrf2 degradation and transcriptional function and downregulates SLC7A11 expression, thereby effectively inhibiting ferroptosis. HO-1 is highly expressed in organs responsible for the degradation of aged red blood cells, and HO-1 in macrophages is involved in the circulation of heme ( Choi and Kim, 2022 ). However, the overexpression of HO-1 promotes cancer cell proliferation and survival ( Drummond et al, 2019 ).…”

Section: Regulatory Mechanism Of Ferritinophagymentioning

confidence: 99%

The critical role of ferritinophagy in human disease

et al. 2022

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Ferritinophagy is a type of autophagy mediated by nuclear receptor activator 4 (NCOA4), which plays a role in inducing ferroptosis by regulating iron homeostasis and producing reactive oxygen species in cells. Under physiological conditions, ferritinophagy maintains the stability of intracellular iron by regulating the release of free iron. Studies have demonstrated that ferritinophagy is necessary to induce ferroptosis; however, under pathological conditions, excessive ferritinophagy results in the release of free iron in large quantities, which leads to lipid peroxidation and iron-dependent cell death, known as ferroptosis. Ferritinophagy has become an area of interest in recent years. We here in review the mechanism of ferritinophagy and its association with ferroptosis and various diseases to provide a reference for future clinical and scientific studies.

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NCI677397 targeting USP24‐mediated induction of lipid peroxidation induces ferroptosis in drug‐resistant cancer cells

Wang,

Wu,

Yang

et al. 2023

Molecular Oncology

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Cancer represents a profound challenge to healthcare systems and individuals worldwide. The development of multiple drug resistance is a major problem in cancer therapy and can result in progression of the disease. In our previous studies, we developed small‐molecule inhibitors targeting ubiquitin‐specific peptidase 24 (USP24) to combat drug‐resistant lung cancer. Recently, we found that the USP24 inhibitor NCI677397 induced ferroptosis, a type of programmed cell death, in drug‐resistant cancer cells by increasing lipid reactive oxygen species (ROS) levels. In the present study, we investigated the molecular mechanisms and found that the targeting of USP24 by NCI677397 increased gene expression of most lipogenesis‐related genes, such as acyl‐CoA synthetase long‐chain family member 4 (ACSL4), and activated autophagy. In addition, the activity of several antioxidant enzymes, such as glutathione peroxidase 4 (GPX4) and dihydrofolate reductase (DHFR), was inhibited by NCI677397 treatment via an increase in protein degradation, thereby inducing lipid ROS production and lipid peroxidation. In summary, we demonstrated that NCI677397 induced a marked increase in lipid ROS levels, subsequently causing lipid peroxidation and leading to the ferroptotic death of drug‐resistant cancer cells. Our study provides new insights into the clinical use of USP24 inhibitors as ferroptosis inducers (FINs) to block drug resistance during chemotherapy.

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Beneficial and Detrimental Roles of Heme Oxygenase-1 in the Neurovascular System

Cited by 23 publications

References 143 publications

Recent Development in the Understanding of Molecular and Cellular Mechanisms Underlying the Etiopathogenesis of Alzheimer’s Disease

Recent Development in the Understanding of Molecular and Cellular Mechanisms Underlying the Etiopathogenesis of Alzheimer’s Disease

The critical role of ferritinophagy in human disease

NCI677397 targeting USP24‐mediated induction of lipid peroxidation induces ferroptosis in drug‐resistant cancer cells

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