12/15 lipoxygenase inhibition suppresses neuroinflammation in a thrombotic permanent cerebral ischemia model

Cakir-Aktas, Canan; Yemişçi, Müge; Bodur, Ebru; Eren-Koçak, Emine; Leyen, Klaus van; Dalkara, Turgay; Karataş, Hülya

doi:10.1016/j.jns.2017.08.2434

Cited by 2 publications

(1 citation statement)

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“…The involvement of 12/15-LOX investigated not only in transient MCAO model but also in permanent cerebral ischemia model in mice (26). In a recent study, FeCl 3 -induced persistent distal MCAO and FeCl 3 -induced ischemia/recanalization with tPA model used in C57Bl6 and CD1 mice and increased immunoreactivity of 12/15-LOX was shown in peri-infarct regions (27).…”

Section: /15 Lipoxygenases In Brain Disordersmentioning

confidence: 99%

12/15 Lipoxygenase as a Therapeutic Target in Stroke

Karataş¹,

Cakir-Aktas²

2019

Archives of Neuropsychiatry

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Lipoxygenases are a family of lipid-oxidizing enzymes, which generate eicosanoids and related compounds from arachidonic acid and other polyunsaturated fatty acids. These metabolites play important roles in physiology and pathogenesis of host defense mechanisms, cardiovascular diseases, cancer, inflammatory, allergic and neurodegenerative diseases. The 12/15-lipoxygenase (LOX) is special in that it can directly oxidize lipid membranes containing polyunsaturated fatty acids, without the preceding action of a phospholipase, leading to the direct attack on membranous organelles, such as mitochondria. The cytotoxic activity of human 12/15-LOX is up-regulated in neurons and endothelial cells especially after a stroke and thought to contribute to both neuronal cell death and blood-brain barrier leakage. The discovery of inhibitors that selectively target recombinant 12/15-LOX in vitro, as well as possessing activity against the murine orthologous ex vivo, could potentially support a novel therapeutic strategy for the treatment of stroke and other brain disorders related to 12/15-LOX. Here we reviewed 12/15-LOX chemistry shortly, and the diseases in which 12/15-LOX has a role in their pathophysiology and recent advances of 12/15-LOX inhibitors as a treatment option for neurological diseases.

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Section: /15 Lipoxygenases In Brain Disordersmentioning

confidence: 99%

12/15 Lipoxygenase as a Therapeutic Target in Stroke

Karataş¹,

Cakir-Aktas²

2019

Archives of Neuropsychiatry

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Arachidonic Acid Metabolites in Neurologic Disorders

Kurşun

Karataş

Barışkaner

et al. 2022

CNSNDDT

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Background & Objective: Arachidonic acid (ARA) is essential for the fluidity, selective permeability, and flexibility of the cell membrane. It is an important factor for the function of all cells, particularly in the nervous system, immune system, and vascular endothelium. ARA, after docosahexaenoic acid, is the second most common polyunsaturated fatty acid in the phospholipids of the nerve cell membrane. ARA metabolites have many kinds of physiologic roles. The major action of ARA metabolites is the promotion of the acute inflammatory response, mediated by the production of pro-inflammatory mediators such as PGE2 and PGI2, followed by the formation of lipid mediators, which have pro-resolving effects. Another important action of ARA derivatives, especially COX, is the regulation of vascular reactivity through PGs and TXA2. There is significant involvement of ARA metabolites in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and neuropsychiatric disorders. ARA derivatives also make an important contribution to acute stroke, global ischemia, subarachnoid hemorrhage, and anticoagulation- related hemorrhagic transformation. Conclusion: In this review, we discuss experimental and human study results of neurologic disorders related to ARA and its metabolites in line with treatment options.

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12/15 lipoxygenase inhibition suppresses neuroinflammation in a thrombotic permanent cerebral ischemia model

Cited by 2 publications

References 0 publications

12/15 Lipoxygenase as a Therapeutic Target in Stroke

12/15 Lipoxygenase as a Therapeutic Target in Stroke

Arachidonic Acid Metabolites in Neurologic Disorders

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