Resolution of Inflammation in Neurodegenerative Diseases: The Role of Resolvins

Abstract

Acute inflammation has been described as a reactive dynamic process, promoted by the secretion of proinflammatory mediators, including lipid molecules like leukotrienes and prostaglandins, and counterbalanced by proresolving mediators including omega-3 polyunsaturated fatty-acid- (PUFA-) derived molecules. The switch from the initiation to the resolution phase of acute inflammatory response is crucial for tissue homeostasis, whereas the failure to resolve early inflammation by specialized proresolving mediators leads to chronic inflammation and tissue damage. Among PUFA-derived proresolving mediators, different eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derivatives have been described, namely, resolvins (resolution phase interaction products), which exert their anti-inflammatory and immune-regulatory activities through specific G-protein-coupled receptors. In recent years, compelling evidence has shown that impairment of resolution of inflammation is a crucial pathogenic hallmark in different neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. This review summarizes current knowledge on the role of resolvins in resolution of inflammation and highlights available evidence showing the neuroprotective potential of EPA- and DHA-derived resolvins (E-series and D-series resolvins, respectively) in neurodegenerative diseases.

Figure 1

Scheme showing the formation of resolvin. DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; RvE1: resolvin E1; LOX: lipoxygenases.

Figure 2

Structure of metabolites. DHA: docosahexaenoic acid; RvD1: resolvin D1; EPA: eicosapentaenoic acid; RvE1: resolvin E1. Citation: https://www.caymanchem.com/product.

Figure 3

Biological role of SPMs in macrophages (a), neutrophils (b), microglia (c), synapse (d), and monocytes (e).

Figure 4

RvE1 blocks NF-κB and TNFα-signaling pathways through binding to ChemR23 (chemerin 23) receptor, induces apoptosis, and decreases migration. AKT: protein kinase B; ERK: extracellular signal-regulated kinases; RvE1: resolvin E1.