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

Physiology

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

33 Scopus citations

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.

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
State	Published - Jan 2020

Bibliographical 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:
© 2020 Elsevier B.V.

Keywords

Alzheimer's disease
Blood brain barrier (BBB)
Ceramide
Fingolimod (FTY720)
GW4869
Sphingomyelin (SM)
Sphingosine-1-phosphate (S1P)
Tricyclic dibenzoazepines (TCA)

ASJC Scopus subject areas

Pharmaceutical Science

Access to Document

10.1016/j.addr.2019.12.003

Cite this

@article{8c174f8bed1d4841a4ab2f6b40401fe7,

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.",

keywords = "Alzheimer's disease, Blood brain barrier (BBB), Ceramide, Fingolimod (FTY720), GW4869, Sphingomyelin (SM), Sphingosine-1-phosphate (S1P), Tricyclic dibenzoazepines (TCA)",

author = "Crivelli, {Simone M.} and Caterina Giovagnoni and Lars Visseren and Scheithauer, {Anna Lena} 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",

month = jan,

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

language = "English",