Sphingolipids in Alzheimer's disease, how can we target them?

Simone M. Crivelli; Caterina Giovagnoni; Lars Visseren; Anna-Lena Scheithauer; Nienke de Wit; Sandra den Hoedt; Mario Losen; Monique T. Mulder; Jochen Walter; Helga E. de Vries; Erhard Bieberich; Pilar Martinez-Martinez

doi:10.1016/j.addr.2019.12.003

Sphingolipids in Alzheimer's disease, how can we target them?

Simone M. Crivelli, Caterina Giovagnoni, Lars Visseren, Anna-Lena Scheithauer, Nienke de Wit, Sandra den Hoedt, Mario Losen, Monique T. Mulder, Jochen Walter, Helga E. de Vries, Erhard Bieberich, Pilar Martinez-Martinez^*

^*Corresponding author for this work

Research output: Contribution to journal › (Systematic) Review article › peer-review

Abstract

Altered levels of sphingolipids and their metabolites in the brain, and the related downstream effects on neuronal homeostasis and the immune system, provide a framework for understanding mechanisms in neurodegenerative disorders and for developing new intervention strategies. In this review we will discuss: the metabolites of sphingolipids that function as second messengers; and functional aberrations of the pathway resulting in Alzheimer's disease (AD) pathophysiology. Focusing on the central product of the sphingolipid pathway ceramide, we describ approaches to pharmacologically decrease ceramide levels in the brain and we argue on how the sphingolipid pathway may represent a new framework for developing novel intervention strategies in AD. We also highlight the possible use of clinical and non-clinical drugs to modulate the sphingolipid pathway and sphingolipid-related biological cascades. (C) 2020 Elsevier B.V. All rights reserved.

Original language	English
Pages (from-to)	214-231
Number of pages	18
Journal	Advanced Drug Delivery Reviews
Volume	159
DOIs	https://doi.org/10.1016/j.addr.2019.12.003
Publication status	Published - 2020

Keywords

Ceramide
Sphingosine-1-phosphate (S1P)
Sphingomyelin (SM)
Alzheimer's disease
Blood brain barrier (BBB)
GW4869
Tricyclic dibenzoazepines (TCA)
Fingolimod (FTY720)
AMYLOID PRECURSOR PROTEIN
NERVE GROWTH-FACTOR
KINASE-C-ZETA
BLOOD-BRAIN-BARRIER
CERAMIDE SYNTHASE 2
SERINE PALMITOYLTRANSFERASE INHIBITOR
MITOCHONDRIAL OUTER-MEMBRANE
CULTURED HIPPOCAMPAL-NEURONS
P75 NEUROTROPHIN RECEPTOR
ANTIGEN-BINDING PROTEIN

Access to Document

10.1016/j.addr.2019.12.003

Cite this

@article{7edd7faca09c4f84acec9c3d0aec8352,

title = "Sphingolipids in Alzheimer's disease, how can we target them?",

abstract = "Altered levels of sphingolipids and their metabolites in the brain, and the related downstream effects on neuronal homeostasis and the immune system, provide a framework for understanding mechanisms in neurodegenerative disorders and for developing new intervention strategies. In this review we will discuss: the metabolites of sphingolipids that function as second messengers; and functional aberrations of the pathway resulting in Alzheimer's disease (AD) pathophysiology. Focusing on the central product of the sphingolipid pathway ceramide, we describ approaches to pharmacologically decrease ceramide levels in the brain and we argue on how the sphingolipid pathway may represent a new framework for developing novel intervention strategies in AD. We also highlight the possible use of clinical and non-clinical drugs to modulate the sphingolipid pathway and sphingolipid-related biological cascades. (C) 2020 Elsevier B.V. All rights reserved.",

keywords = "Ceramide, Sphingosine-1-phosphate (S1P), Sphingomyelin (SM), Alzheimer's disease, Blood brain barrier (BBB), GW4869, Tricyclic dibenzoazepines (TCA), Fingolimod (FTY720), AMYLOID PRECURSOR PROTEIN, NERVE GROWTH-FACTOR, KINASE-C-ZETA, BLOOD-BRAIN-BARRIER, CERAMIDE SYNTHASE 2, SERINE PALMITOYLTRANSFERASE INHIBITOR, MITOCHONDRIAL OUTER-MEMBRANE, CULTURED HIPPOCAMPAL-NEURONS, P75 NEUROTROPHIN RECEPTOR, ANTIGEN-BINDING PROTEIN",

author = "Crivelli, {Simone M.} and Caterina Giovagnoni and Lars Visseren and Anna-Lena Scheithauer and {de Wit}, Nienke and {den Hoedt}, Sandra and Mario Losen and Mulder, {Monique T.} and Jochen Walter and {de Vries}, {Helga E.} and Erhard Bieberich and Pilar Martinez-Martinez",

note = "Funding Information: This work was supported by grants to SMC, NMdW, SdH, MTM, JW, AR, PMM, and HEV from ZonMw Memorabel program (projectnr: 733050105 ). PMM is also supported by the International Foundation for Alzheimer Research (ISAO) (projectnr: 14545 ). EB is supported by R01AG034389 , R01NS095215 , VA grant I01 BX003643 and NSF 1615874 . SMC received a travel grant support from Alzheimer Netherlands to visit the laboratory of EB, University of Kentucky , Lexington KY, USA. Publisher Copyright: {\textcopyright} 2020 Elsevier B.V.",

year = "2020",

doi = "10.1016/j.addr.2019.12.003",

language = "English",

volume = "159",

pages = "214--231",

journal = "Advanced Drug Delivery Reviews",