TY - JOUR
T1 - The Role of Sphingolipids and Specialized Pro-Resolving Mediators in Alzheimer’s Disease
AU - de Wit, Nienke M.
AU - Mol, Kevin
AU - Rodríguez-Lorenzo, Sabela
AU - de Vries, Helga E.
AU - Kooij, Gijs
N1 - Funding Information: This work was supported by a grant from IMI (807015 to NW), a grant from the Dutch MS Research Foundation (20-1087 MS to SRL), as well as a grant from the Dutch Research Council (NWO Vidi grant 91719305 to GK). Publisher Copyright: © Copyright © 2021 de Wit, Mol, Rodríguez-Lorenzo, de Vries and Kooij. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/29
Y1 - 2021/1/29
N2 - Alzheimer’s disease (AD) is the leading cause of dementia worldwide giving rise to devastating forms of cognitive decline, which impacts patients’ lives and that of their proxies. Pathologically, AD is characterized by extracellular amyloid deposition, neurofibrillary tangles and chronic neuroinflammation. To date, there is no cure that prevents progression of AD. In this review, we elaborate on how bioactive lipids, including sphingolipids (SL) and specialized pro-resolving lipid mediators (SPM), affect ongoing neuroinflammatory processes during AD and how we may exploit them for the development of new biomarker panels and/or therapies. In particular, we here describe how SPM and SL metabolism, ranging from ω-3/6 polyunsaturated fatty acids and their metabolites to ceramides and sphingosine-1-phosphate, initiates pro- and anti-inflammatory signaling cascades in the central nervous system (CNS) and what changes occur therein during AD pathology. Finally, we discuss novel therapeutic approaches to resolve chronic neuroinflammation in AD by modulating the SPM and SL pathways.
AB - Alzheimer’s disease (AD) is the leading cause of dementia worldwide giving rise to devastating forms of cognitive decline, which impacts patients’ lives and that of their proxies. Pathologically, AD is characterized by extracellular amyloid deposition, neurofibrillary tangles and chronic neuroinflammation. To date, there is no cure that prevents progression of AD. In this review, we elaborate on how bioactive lipids, including sphingolipids (SL) and specialized pro-resolving lipid mediators (SPM), affect ongoing neuroinflammatory processes during AD and how we may exploit them for the development of new biomarker panels and/or therapies. In particular, we here describe how SPM and SL metabolism, ranging from ω-3/6 polyunsaturated fatty acids and their metabolites to ceramides and sphingosine-1-phosphate, initiates pro- and anti-inflammatory signaling cascades in the central nervous system (CNS) and what changes occur therein during AD pathology. Finally, we discuss novel therapeutic approaches to resolve chronic neuroinflammation in AD by modulating the SPM and SL pathways.
KW - Alzheimer’s disease
KW - bioactive lipids
KW - ceramide
KW - neuroinflammation
KW - specialized pro-resolving mediator
KW - sphingolipids
KW - sphingosine-1-phosphate
UR - http://www.scopus.com/inward/record.url?scp=85101046621&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fimmu.2020.620348
DO - https://doi.org/10.3389/fimmu.2020.620348
M3 - Review article
C2 - 33633739
SN - 1664-3224
VL - 11
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 620348
ER -