1. Sphingolipids in Alzheimer's disease, how can we target them?
- Author
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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, and Internal Medicine
- Subjects
Ceramide ,CERAMIDE SYNTHASE 2 ,Pharmaceutical Science ,02 engineering and technology ,Disease ,Biology ,Blood–brain barrier ,Fingolimod (FTY720) ,Tricyclic dibenzoazepines (TCA) ,ANTIGEN-BINDING PROTEIN ,03 medical and health sciences ,chemistry.chemical_compound ,KINASE-C-ZETA ,Alzheimer Disease ,Blood brain barrier (BBB) ,medicine ,Amyloid precursor protein ,Animals ,Humans ,Sphingosine-1-phosphate (S1P) ,030304 developmental biology ,Neurons ,GW4869 ,Sphingolipids ,0303 health sciences ,Cell Death ,BLOOD-BRAIN-BARRIER ,NERVE GROWTH-FACTOR ,Ceramide synthase 2 ,Alzheimer's disease ,MITOCHONDRIAL OUTER-MEMBRANE ,021001 nanoscience & nanotechnology ,Sphingolipid ,AMYLOID PRECURSOR PROTEIN ,carbohydrates (lipids) ,medicine.anatomical_structure ,Sphingomyelin (SM) ,chemistry ,Blood-Brain Barrier ,Second messenger system ,SERINE PALMITOYLTRANSFERASE INHIBITOR ,CULTURED HIPPOCAMPAL-NEURONS ,biology.protein ,P75 NEUROTROPHIN RECEPTOR ,lipids (amino acids, peptides, and proteins) ,0210 nano-technology ,Neuroscience ,Function (biology) - 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.
- Published
- 2020
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