Current and Future Directions for Targeting Lipoxin A4 in Alzheimer’s Disease

Abstract

Neuroinflammation has been implicated in Alzheimer's disease onset and progression. Chronic neuroinflammation is initiated by amyloid-ß-activated microglial cells that secrete immuno-modulatory molecules within the brain and into the vasculature. Inflammation is normally self-limiting and actively resolves by 'switching off' the generation of pro-inflammatory mediators and by non-phlogistic clearance of spent cells and their debris to restore tissue homeostasis. Deficits in these anti-inflammatory/pro-resolution pathways may predispose to the development of chronic inflammation. The synthesis of endogenous lipid mediators from arachidonic acid, lipoxins via cyclooxygenase 2 and lipoxygenases, and conversion of exogenous polyunsaturated fatty acids, namely docosahexaenoic acid and eicosapentaenoic acid, to resolvins contributes to effective, timely resolution of acute inflammation. Work by Xiuzhe et al., 2020 in the Journal of Alzheimer's Disease reported that plasma level of LXA4 is related to cognitive status in ischemic stroke patients suggesting that decreased LXA4 may be a potential risk factor for post post-stroke cognitive impairment. As evident by recent clinical trials and development of drug analogues, there is recent drive to search for lipoxin analogues as therapeutics for inflammatory diseases. Understanding how bioactive lipid signaling is involved in resolution will increase our understanding of controlling inflammation and may facilitate the discovery of new classes of therapeutic pro-resolution agents for evaluation in AD prevention studies.

Publication DOI: https://doi.org/10.3233/jad-210121
Divisions: College of Health & Life Sciences > Aston Medical School
College of Health & Life Sciences > Aston Medical School > Translational Medicine Research Group (TMRG)
Additional Information: The final publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-210121. Dias, I. H. K., & Griffiths, H. R. (2021). Current and Future Directions for Targeting Lipoxin A4 in Alzheimer’s Disease. Journal of Alzheimer's disease. https://doi.org/10.3233/jad-210121
Uncontrolled Keywords: Alzheimer's disease,LXA4 drug analogues,Lipoxin A4,lipoxygenase,neuroinflammation,pro-resolution,stroke,therapy,Neuroscience(all),Clinical Psychology,Geriatrics and Gerontology,Psychiatry and Mental health
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Related URLs: https://content ... sease/jad210121 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Review article
Published Date: 2021
Published Online Date: 2021-03-11
Accepted Date: 2021-02-22
Authors: Dias, Irundika H.K. (ORCID Profile 0000-0002-6620-8221)
Griffiths, Helen R.

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