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

Frontiers in Aging Neuroscience

Jiri Adamec¹  Vivien Marmelat²  Alfred Fisher³  Erin Cameron-Smith⁴  John Bertoni⁴  Danish Bhatti⁴  Jenna Wuebker⁵  Arzu Ulu⁶  Corrine Hanson⁷  Ka-Chun Siu⁷  Jana Ponce⁷ 

[1] Department of Biochemistry, College of Arts and Sciences, University of Nebraska - Lincoln, Lincoln, NE, United States;Department of Biomechanics, College of Education, Health, and Human Sciences, University of Nebraska - Omaha, Omaha, NE, United States;Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, United States;Department of Neurological Sciences, College of Medicine, University of Nebraska Medical Center, Omaha, NE, United States;Department of Pharmaceutical and Nutrition Care, Nebraska Medicine, Omaha, NE, United States;Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA, United States;Division of Medical Nutrition Education, College of Allied Health Professions, University of Nebraska Medical Center, Omaha, NE, United States;

关键词: neurodegenerative disorder;    Parkinson’s disease;    Alzheimer’s disease;    neuroinflammation;    specialized pro-resolving lipid mediator (SPM);    omega-3 fatty acids;   

DOI  :  10.3389/fnagi.2022.780811

来源: DOAJ

【 摘 要 】

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 pro-inflammatory 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 PUFA-derived 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.

【 授权许可】

Unknown