Role of Specialized Pro-resolving Mediators in Reducing Neuroinflammation in Neurodegenerative Disorders

Authors

Jana Ponce, University of Nebraska Medical Center
Arzu ulu, University of California
Corrine Hanson, University of Nebraska Medical Center
Erin Cameron-Smith, University of Nebraska Medical Center
Jenna Wuebker, Nebraska Medicine
John Bertoni, University of Nebraska Medical Center
Alfred Fisher, University of Nebraska Medical Center
Ka-Chun Siu, University of Nebraska Medical Center
Vivien Marmelat, University of Nebraska at Omaha
Jiri Adamec, University of Nebraska - Lincoln
Danish Bhatti, University of Nebraska Medical Center

Document Type

Article

Date of this Version

2-17-2022

Citation

Ponce J, Ulu A, Hanson C, Cameron-Smith E, Bertoni J, Wuebker J, Fisher A, Siu K-C, Marmelat V, Adamec J and Bhatti D (2022) Role of Specialized Pro-resolving Mediators in Reducing Neuroinflammation in Neurodegenerative Disorders. Front. Aging Neurosci. 14:780811. doi: 10.3389/fnagi.2022.780811

Comments

© 2022 Ponce, Ulu, Hanson, Cameron-Smith, Bertoni, Wuebker, Fisher, Siu, Marmelat, Adamec and Bhatti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)

Abstract

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are neurodegenerative disorders that affect millions of individuals worldwide. As incidence of these conditions increases with age, there will undoubtedly be an increased prevalence of cases in the near future. Neuroinflammation is a hallmark in the development and progression of neurodegenerative diseases and prevention or resolution of chronic neuroinflammation may represent a novel approach to treatment. The present review highlights the potential of the anti-inflammatory and pro-resolving effects of polyunsaturated fatty acid (PUFA)- derived mediators (Specialized Pro-resolving Mediators—SPM) in neurodegenerative disorders. PUFA-derived SPM are biosynthesized in response to chemicals produced from acute inflammatory responses. Preclinical studies from both AD and PD models suggest a dysregulation of SPM and their receptors in neurological disorders. Decreased SPM may be due to inadequate substrate, an imbalance between SPM and proinflammatory mediators or a disruption in SPM synthesis. SPMs hold great promise for neuroprotection in AD by altering expression of pro-inflammatory genes, modulating macrophage function, serving as a biomarker for AD status, and promoting resolution of neuroinflammation. In PD, data suggest SPM are able to cross the blood-brain barrier, inhibit microglial activation and decrease induced markers of inflammation, possibly as a result of their ability to downregulate NFκB signaling pathways. Several in vivo and in vitro studies suggest a benefit from administration of SPMs in both neurodegenerative disorders. However, extrapolation of these outcomes to humans is difficult as no models are able to replicate all features of AD or PD. Minimal data evaluating these PUFAderived metabolites in humans with neurodegenerative disorders are available and a gap in knowledge exists regarding behavior of SPM and their receptors in patients with these conditions. There is also large gap in our knowledge regarding which lipid mediator would be most effective in which model of AD or PD and how dietary intake or supplementation can impact SPM levels. Future direction should include focused, translational efforts to investigate SPM as an add-on (in addition to standard treatment) or as standalone agents in patients with neurodegenerative disorders.