Alzheimer’s Disease and Specialized Pro-Resolving Lipid Mediators: Do MaR1, RvD1, and NPD1 Show Promise for Prevention and Treatment?

Abstract

Alzheimer’s disease (AD) is a common neurodegenerative disease and a major contributor to progressive cognitive impairment in an aging society. As the pathophysiology of AD involves chronic neuroinflammation, the resolution of inflammation and the group of lipid mediators that actively regulate it—i.e., specialized pro-resolving lipid mediators (SPMs)—attracted attention in recent years as therapeutic targets. This review focuses on the following three specific SPMs and summarizes their relationships to AD, as they were shown to effectively address and reduce the risk of AD-related neuroinflammation: maresin 1 (MaR1), resolvin D1 (RvD1), and neuroprotectin D1 (NPD1). These three SPMs are metabolites of docosahexaenoic acid (DHA), which is contained in fish oils and is thus easily available to the public. They are expected to become incorporated into promising avenues for preventing and treating AD in the future.

Maresin-1 and Inflammatory Disease

“…In an animal model of Alzheimer's disease, amyloid-β42 protein was believed to play a central role in the pathogenesis of Alzheimer's disease by causing an inflammatory response in the amyloid-β42 proteins deposited in the brain. Maresin-1 has been shown to decrease the production of proinflammatory cytokines, such as TNF-α and IL-6, while increasing the secretion of the anti-inflammatory cytokines, IL-2 and IL-10, by the regulation of the amyloid-β42 protein [34][35][36].…”

Why Have the Benefits of DHA Not Been Borne Out in the Treatment and Prevention of Alzheimer’s Disease? A Narrative Review Focused on DHA Metabolism and Adipose Tissue

“…AD pathogenesis is also associated with chronic neuroinflammation [ 49 ]. DHA and its downstream metabolites, which form a subset of ‘Specialized Pro-resolving Mediators’ (SPMs), act to inhibit inflammatory signaling, inhibit amyloid-beta associated apoptosis and promote anti-apoptotic gene expression [ 50 ], to foster the return of injured tissues to pre-injury homeostasis [ 27 , 51 , 52 ]. The prototypical SPM of the central nervous system, neuroprotectin D1 (NPD1) is produced via lipoxygenation of DHA after oxidative insults and ischemia-related injury [ 53 ], and induces pro-survival and anti-inflammatory signaling [ 54 ].…”

Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase and ethanolamides metabolism with Alzheimer’s disease

“…Changes in circulating lipid mediators in relation to AD were previously reported. Particularly, several oxylipins of the acute in ammation pathway were reportedly elevated in AD (14,15) and pro-resolving (quenching activated in ammatory signal) lipid mediators have been suggested as potential treatment for AD (16). Speci c changes in bile acids metabolism, including a decrease in primary and an increase in secondary metabolites were also observed in AD subjects (17) and differences in bile acids clearance for cholesterol pathway were reported in AD (18).…”