12/15 lipoxygenase: A crucial enzyme in diverse types of cell death

Li, Qiu-Qi; Qin, Li; Jia, Ji-Ning; Liu, Zhao‐Qian; Zhou, Hong‐Hao; Mao, Xiao‐Yuan

doi:10.1016/j.neuint.2018.04.002

Cited by 37 publications

(28 citation statements)

References 108 publications

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“…Ferroptosis is an iron-dependent mode of regulated cell death that is characterized by the accumulation of lethal lipid-based ROS (Dixon et al, 2012; Li Q.-Q. et al, 2018).…”

Section: Is Redox-associated Ferroptosis Important In Epilepsy?mentioning

confidence: 99%

Redox-Related Neuronal Death and Crosstalk as Drug Targets: Focus on Epilepsy

2019

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Cell death has a vital role in embryonic development and organismal homeostasis. Biochemical, pharmacological, behavioral, and electrophysiological evidences support the idea that dysregulation of cell death programs are involved in neuropathological conditions like epilepsy. The brain is particularly vulnerable to oxidative damage due to higher oxygen consumption and lower endogenous antioxidant defense than other bodily organ. Thus, in this review, we focused on the comprehensive summarization of evidence for redox-associated cell death pathways including apoptosis, autophagy, necroptosis, and pyroptosis in epilepsy and the oxidative stress-related signaling in this process. We specially proposed that the molecular crosstalk of various redox-linked neuronal cell death modalities might occur in seizure onset and/or epileptic conditions according to the published data. Additionally, abundance of polyunsaturated fatty acids in neuronal membrane makes the brain susceptible to lipid peroxidation. This presumption was then formalized in the proposal that ferroptosis, a novel type of lipid reactive oxygen species (ROS)-dependent regulatory cell death, is likely to be a critical mechanism for the emergence of epileptic phenotype. Targeting ferroptosis process or combination treatment with multiple cell death pathway inhibitors may shed new light on the therapy of epilepsy.

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“…Ferroptosis is an iron-dependent mode of regulated cell death that is characterized by the accumulation of lethal lipid-based ROS (Dixon et al, 2012; Li Q.-Q. et al, 2018).…”

Section: Is Redox-associated Ferroptosis Important In Epilepsy?mentioning

confidence: 99%

Redox-Related Neuronal Death and Crosstalk as Drug Targets: Focus on Epilepsy

2019

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“…In turn, low levels of the 15-LOX-2 isoform and consequently decreased 15-HETE formation were found as distinctive alterations of AA metabolism in prostate cancer cells. 15-LOX enzymes may exert anti-tumoral effects in particular types of tumors (Klil-Drori and Ariel, 2013) by promoting apoptosis, ferroptosis, or autophagy (Li et al, 2018). For instance, 15-LOX-1 contributes to inflammation resolution through its 13-HODE product (13-hydroxyoctadecadienoic acid) derived from linoleic acid, and has an important role in the terminal differentiation of normal cells.…”

Section: Ndga Exerts Anti-cancer Effects By Lox Inhibitionmentioning

confidence: 99%

Nordihydroguaiaretic Acid: From Herbal Medicine to Clinical Development for Cancer and Chronic Diseases

et al. 2020

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Nordihydroguaiaretic acid (NDGA) is a phenolic lignan obtained from Larrea tridentata, the creosote bush found in Mexico and USA deserts, that has been used in traditional medicine for the treatment of numerous diseases such as cancer, renal, cardiovascular, immunological, and neurological disorders, and even aging. NDGA presents two catechol rings that confer a very potent antioxidant activity by scavenging oxygen free radicals and this may explain part of its therapeutic action. Additional effects include inhibition of lipoxygenases (LOXs) and activation of signaling pathways that impinge on the transcription factor Nuclear Factor Erythroid 2-related Factor (NRF2). On the other hand, the oxidation of the catechols to the corresponding quinones my elicit alterations in proteins and DNA that raise safety concerns. This review describes the current knowledge on NDGA, its targets and side effects, and its synthetic analogs as promising therapeutic agents, highlighting their mechanism of action and clinical projection towards therapy of neurodegenerative, liver, and kidney disease, as well as cancer.

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“…In animal models of brain ischemia, 12/15-LOX expression increases, and the inhibition of 12/15-LOX can reduce the rate of the neuronal death, improving recovery (Karatas et al, 2018). Previous studies have shown that suppressing 12/15-LOX can result in the inhibition of ferroptosis (Li et al, 2018). To date, it remains unclear whether multiple subtypes work in conjunction or whether only one subtype is sufficient to initiate lipid peroxidation and ferroptosis, necessitating further study.…”

Section: Inhibition Of Lox Can Inhibit Ferroptosis and Improve Cerebrmentioning

confidence: 99%

Cross Talk Between Ferroptosis and Cerebral Ischemia

et al. 2020

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Recently, ferroptosis has been revealed as a new form of regulated cell death. Distinct from apoptosis and necrosis, ferroptosis is evoked by iron-dependent lipid peroxidation. Furthermore, the metabolism of iron, lipids, and amino acids plays a significant regulatory role in ferroptosis, which can be reversed by glutathione peroxidase 4 and ferroptosis suppressor protein 1. Ferroptosis is implicated in the onset and development of numerous neurological diseases. Emerging studies have reported that ferroptosis induces and aggravates brain tissue damage following cerebral ischemia, whereas inhibition of ferroptosis dramatically attenuates induced damage. In this review, we have summarized the mechanistic relationship between ferroptosis and cerebral ischemia, including through iron overload, downregulation of glutathione peroxidase 4, and upregulation of lipid peroxidation. Although considerable attention has been paid to the effect of ferroptosis on cerebral ischemic injury, specific mechanisms need to be experimentally confirmed, including how cerebral ischemia induces ferroptosis and how ferroptosis deteriorates cerebral ischemia.

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12/15 lipoxygenase: A crucial enzyme in diverse types of cell death

Cited by 37 publications

References 108 publications

Redox-Related Neuronal Death and Crosstalk as Drug Targets: Focus on Epilepsy

Redox-Related Neuronal Death and Crosstalk as Drug Targets: Focus on Epilepsy

Nordihydroguaiaretic Acid: From Herbal Medicine to Clinical Development for Cancer and Chronic Diseases

Cross Talk Between Ferroptosis and Cerebral Ischemia

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