Fairweather Friends: Evidence of Lipoxin Dysregulation in Neurodegeneration

• Published in: Molecular nutrition & food research 2020-01, Vol.64 (4), p.e1801076-e1801076
• Main Authors: Kim, Changmo, Livne-Bar, Izhar, Gronert, Karsten, Sivak, Jeremy M.
• Format: Article
• Language: English
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201801076

Lipoxins (LXs) are autacoids; specialized proresolving lipid mediators (SPMs) acting locally in a paracrine or autocrine fashion. They belong to a complex superfamily of dietary small polyunsaturated fatty acid (PUFA)- metabolites, which direct potent cellular responses to resolve inflammation and restore tissue homeostasis. Together, these SPM activities have been intensely studied in systemic inflammation and acute injury or infection, but less is known about LX signaling and activities in the central nervous system. LXs are derived from arachidonic acid (AA), an omega-6 PUFA. In addition to well established roles in systemic inflammation resolution, they have increasingly become implicated in regulating neuroinflammatory and neurodegenerative processes. In particular, chronic inflammation plays a central role in Alzheimer’s disease (AD) etiology, and dysregulated LX production and activities have been reported in a variety of AD rodent models and clinical tissue samples, yet with complex and sometimes conflicting results. In addition, we recently reported reduced LX production following retinal injury, and demonstrated an intriguing direct neuronal activity promoting survival and homeostasis in retinal and cortical neurons. Here we review and clarify this growing literature and suggest new research directions to further elaborate the role of lipoxins in neurodegeneration. Lipoxins (LXs) are lipid mediators derived from arachidonic acid (AA), an omega-6 PUFA, and are potent signals to resolve inflammation and restore tissue homeostasis. LXs are increasingly implicated in neuroinflammation and neurodegeneration through dysregulated lipoxygenase (LOX) activity and receptor signaling, as well as directly affecting neuronal survival. We synthesize and clarify this growing literature.