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Vol. 26, No. 1, 2010
Issue release date: 2010
Section title: Review
Cell Physiol Biochem 2010;25:9–20
(DOI:10.1159/000315101)

Functional Inhibitors of Acid Sphingomyelinase (FIASMAs): A Novel Pharmacological Group of Drugs with Broad Clinical Applications

Kornhuber J. · Tripal P. · Reichel M. · Mühle C. · Rhein C. · Muehlbacher M. · Groemer T.W. · Gulbins E.
Department of Psychiatry and Psychotherapy, University of Erlangen,1Department of Molecular Biology, University of Duisburg-Essen

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Abstract

Acid sphingomyelinase (ASM) is an important lipid-metabolizing enzyme cleaving sphingomyelin to ceramide, mainly within lysosomes. Acid ceramidase (AC) further degrades ceramide to sphingosine which can then be phosphorylated to sphingosine-1-phosphate. Ceramide and its metabolite sphingosine-1-phosphate have been shown to antagonistically regulate apoptosis, cellular differentiation, proliferation and cell migration. Inhibitors of ASM or AC therefore hold promise for a number of new clinical therapies, e.g. for Alzheimer’s disease and major depression on the one hand and cancer on the other. Inhibitors of ASM have been known for a long time. Cationic amphiphilic substances induce the detachment of ASM protein from inner lysosomal membranes with its consecutive inactivation, thereby working as functional inhibitors of ASM. We recently experimentally identified a large number of hitherto unknown functional inhibitors of ASM and determined specific physicochemical properties of such cationic amphiphilic substances that functionally inhibit ASM. We propose the acronym “FIASMA” (Functional Inhibitor of Acid SphingoMyelinAse) for members of this large group of compounds with a broad range of new clinical indications. FIASMAs differ markedly with respect to molecular structure and current clinical indication. Most of the available FIASMAs are licensed for medical use in humans, are minimally toxic and may therefore be applied for disease states associated with increased activity of ASM.


  

Author Contacts

Johannes Kornhuber, MD
Department of Psychiatry and Psychotherapy, University of Erlangen
Schwabachanlage 6, 91054 Erlangen (Germany)
Tel. +49-9131-853-4160, Fax +49-9131-853-4862
E-Mail Johannes.Kornhuber@uk-erlangen.de

  

Article Information

Accepted: November 13, 2009
Published online: May 18, 2010
Number of Print Pages : 12

  

Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry andPharmacology)

Vol. 26, No. 1, Year 2010 (Cover Date: 2010)

Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (Print), eISSN: 1421–9778 (Online)

For additional information: http://www.karger.com/journals/cpb


Article / Publication Details

First-Page Preview
Abstract of Review

Accepted: 11/13/2009
Published online: 5/18/2010

Number of Print Pages: 12
Number of Figures: 0
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

For additional information: http://www.karger.com/CPB


Copyright / Drug Dosage

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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