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Exploring the molecular approach of COX and LOX in Alzheimer’s and Parkinson’s disorder

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Abstract

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.

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Acknowledgements

The authors would like to thank Chitkara College of Pharmacy, Chitkara University, Punjab, India for providing basic facilities for completion of the article.

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  1. Tapan Behl and Ishnoor Kaur contributed equally to this work.

Authors and Affiliations

  1. Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India

    Arun Kumar, Tapan Behl & Ishnoor Kaur

  2. Department of Psychiatry, Yale School of Medicine, Yale University, New Haven, CT, 06511, USA

    Sumit Jamwal

  3. Institute of Plant Sciences, Volcani Center, Agricultural Research Organisation (ARO), Rishon LeTsiyon, Israel

    Archit Sood

  4. Department of Pharmacology, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151001, India

    Puneet Kumar

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AK: Conceived the idea and wrote the first Draft, TB: Improved the article, SJ: Review of Literature, IK: Writing and improvement of article, AS: Proof Read, PK: Proof Read and improvement of article.

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Kumar, A., Behl, T., Jamwal, S. et al. Exploring the molecular approach of COX and LOX in Alzheimer’s and Parkinson’s disorder. Mol Biol Rep 47, 9895–9912 (2020). https://doi.org/10.1007/s11033-020-06033-x

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  • DOI: https://doi.org/10.1007/s11033-020-06033-x

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