| Literature DB >> 31911096 |
Simone M Crivelli1, Caterina Giovagnoni2, Lars Visseren2, Anna-Lena Scheithauer3, Nienke de Wit4, Sandra den Hoedt5, Mario Losen2, Monique T Mulder5, Jochen Walter3, Helga E de Vries6, Erhard Bieberich7, Pilar Martinez-Martinez8.
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.Entities:
Keywords: Alzheimer's disease; Blood brain barrier (BBB); Ceramide; Fingolimod (FTY720); GW4869; Sphingomyelin (SM); Sphingosine-1-phosphate (S1P); Tricyclic dibenzoazepines (TCA)
Year: 2020 PMID： 31911096 DOI： 10.1016/j.addr.2019.12.003
Source DB: PubMed Journal: Adv Drug Deliv Rev ISSN： 0169-409X Impact factor: 15.470