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

Authors :: Erhard Bieberich
Jochen Walter
Sandra den Hoedt
Monique T. Mulder
Mario Losen
Caterina Giovagnoni
Lars Visseren
Anna-Lena Scheithauer
Pilar Martinez-Martinez
Simone M. Crivelli
Nienke M. de Wit
Helga E. de Vries
Internal Medicine
Source :: Crivelli, S M, Giovagnoni, C, Visseren, L, Scheithauer, A-L, de Wit, N, den Hoedt, S, Losen, M, Mulder, M T, Walter, J, de Vries, H E, Bieberich, E & Martinez-Martinez, P 2020, ' Sphingolipids in Alzheimer's disease, how can we target them? ', Advanced Drug Delivery Reviews, vol. 159, pp. 214-231 . https://doi.org/10.1016/j.addr.2019.12.003, Advanced Drug Delivery Reviews, 159, 214-231. Elsevier
Publication Year :: 2020
Publisher :: Elsevier, 2020.
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.