Exploring the molecular approach of COX and LOX in Alzheimer’s and Parkinson’s disorder
| Autor: | Ishnoor Kaur, Puneet Kumar, Archit Sood, Arun Kumar, Sumit Jamwal, Tapan Behl |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Docosahexaenoic Acids Pharmacology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Phospholipase A2 Alzheimer Disease Genetics Animals Humans Medicine Molecular Biology Neuroinflammation Lipoxin Arachidonic Acid biology business.industry Brain Parkinson Disease General Medicine Lipid signaling Lipoxygenases Lipid Metabolism 030104 developmental biology chemistry Prostaglandin-Endoperoxide Synthases Docosahexaenoic acid 030220 oncology & carcinogenesis biology.protein lipids (amino acids peptides and proteins) Cytokine secretion Arachidonic acid business Eicosanoid Production |
| Zdroj: | Molecular Biology Reports. 47:9895-9912 |
| ISSN: | 1573-4978 0301-4851 |
| Popis: | Neuroinflammation is well established biomarker for the major neurodegenerative like Alzheimer's disease (AD) and Parkinson's disease (PD). Cytokines/chemokines excite phospholipase A2 and cyclooxygenases (COX), facilitating the release of arachidonic acid (AA) and docosahexaenoic acid (DHA) from membrane glycerophospholipids, in which the former is oxidized to produce pro-inflammatory eicosanoids (prostaglandins, leukotrienes and thromboxane's), which intensify the neuroinflammatory events in the brain. Similarly, resolvins and neuroprotectins are the metabolized products of docosahexaenoic acid, which exert an inhibitory effect on the production of eicosanoids. Furthermore, an oxidized product of arachidonic acid, lipoxin, is generated via 5-lipoxygenase (5-LOX) pathway, and contributes to the resolution of inflammation, along with anti-inflammatory actions. Moreover, DHA and its lipid mediators inhibit neuroinflammatory responses by blocking NF-κB, inhibiting eicosanoid production, preventing cytokine secretion and regulating leukocyte trafficking. Various epidemiological studies reported, elevated levels of COX-2 enzyme in patients with AD and PD, indicating its role in progression of the disease. Similarly, enhanced levels of 5-LOX and 12/15-LOX in PD models represent their role brain disorders, where the former is expressed in AD patients and the latter exhibits it involvement in PD. The present review elaborates the role of AA, DHA, eicosanoids and docosanoids, along with COX and LOX pathway which provides an opportunity to the researchers to understand the role of these lipid mediators in neurological disorders (AD and PD). The information gathered from the review will aid in facilitating the development of appropriate therapeutic options targeting COX and LOX pathway. |
| Databáze: | OpenAIRE |
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