TY  - JOUR
A1  - Hasan, Ahmed Abdallah Abdalrahman Mohamed
A1  - von Websky, Karoline
A1  - Reichetzeder, Christoph
A1  - Tsuprykov, Oleg
A1  - Gaballa, Mohamed Mahmoud Salem Ahmed
A1  - Guo, Jingli
A1  - Zeng, Shufei
A1  - Delic, Denis
A1  - Tammen, Harald
A1  - Klein, Thomas
A1  - Kleuser, Burkhard
A1  - Hocher, Berthold
T1  - Mechanisms of GLP-1 receptor-independent renoprotective effects of the dipeptidyl peptidase type 4 inhibitor linagliptin in GLP-1 receptor knockout mice with 5/6 nephrectomy
JF  - Kidney international : official journal of the International Society of Nephrology
N2  - Dipeptidyl peptidase type 4 (DPP-4) inhibitors were reported to have beneficial effects in experimental models of chronic kidney disease. The underlying mechanisms are not completely understood. However, these effects could be mediated via the glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP1R) pathway. Here we investigated the renal effects of the DPP-4 inhibitor linagliptin in Glp1r-/- knock out and wild-type mice with 5/6 nephrectomy (5/6Nx). Mice were allocated to groups: sham + wild type + placebo; 5/6Nx+ wild type + placebo; 5/6Nx+ wild type + linagliptin; sham + knock out+ placebo; 5/6Nx + knock out+ placebo; 5/6Nx + knock out+ linagliptin. 5/6Nx caused the development of renal interstitial fibrosis, significantly increased plasma cystatin C and creatinine levels and suppressed renal gelatinase/collagenase, matrix metalloproteinase-1 and -13 activities; effects counteracted by linagliptin treatment in wildtype and Glp1r-/- mice. Two hundred ninety-eight proteomics signals were differentially regulated in kidneys among the groups, with 150 signals specific to linagliptin treatment as shown by mass spectrometry. Treatment significantly upregulated three peptides derived from collagen alpha-1(I), thymosin beta 4 and heterogeneous nuclear ribonucleoprotein Al (HNRNPA1) and significantly downregulated one peptide derived from Y box binding protein-1 (YB-1). The proteomics results were further confirmed using western blot and immunofluorescence microscopy. Also, 5/6Nx led to significant up-regulation of renal transforming growth factor-beta 1 and pSMAD3 expression in wild type mice and linagliptin significantly counteracted this up-regulation in wild type and GIplr-/- mice. Thus, the renoprotective effects of linagliptin cannot solely be attributed to the GLP-1/GLP1R pathway, highlighting the importance of other signaling pathways (collagen I homeostasis, HNRNPA1,YB-1,thymosin beta 4 and TGF-beta 1) influenced by DPP-4 inhibition.
KW  - chronic kidney disease
KW  - collagen I
KW  - fibrosis
KW  - Glp1r(-/-) mice
KW  - HNRNPA1
KW  - linagliptin
KW  - proteomic analysis
KW  - TGF-beta 1
KW  - thymosin beta 4
KW  - YB-1
Y1  - 2019
U6  - https://doi.org/10.1016/j.kint.2019.01.010
SN  - 0085-2538
SN  - 1523-1755
VL  - 95
IS  - 6
SP  - 1373
EP  - 1388
PB  - Elsevier
CY  - New York
ER  - 
TY  - GEN
A1  - Rancan, Fiorenza
A1  - Volkmann, Hildburg
A1  - Giulbudagian, Michael
A1  - Schumacher, Fabian
A1  - Stanko, Jessica Isolde
A1  - Kleuser, Burkhard
A1  - Blume-Peytavi, Ulrike
A1  - Calderón, Marcelo
A1  - Vogt, Annika
T1  - Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels
T2  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was investigated in ex vivo abdominal and breast skin, while different methods for skin barrier disruption were investigated to improve skin permeability or simulate inflammatory conditions with compromised skin barrier. The amount of penetrated tacrolimus was measured in skin extracts by liquid chromatography tandem-mass spectrometry (LC-MS/MS), whereas the inflammatory markers IL-6 and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). Higher amounts of tacrolimus penetrated in breast as compared to abdominal skin or in barrier-disrupted as compared to intact skin, confirming that the stratum corneum is the main barrier for tacrolimus skin penetration. The anti-proliferative effect of the penetrated drug was measured in skin tissue/Jurkat cells co-cultures. Interestingly, tNGs exhibited similar anti-proliferative effects as the 0.1% tacrolimus ointment. We conclude that polyglycerol-based nanogels represent an interesting alternative to paraffin-based formulations for the treatment of inflammatory skin conditions.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1339 
KW  - tacrolimus formulation
KW  - nanogels
KW  - skin penetration
KW  - drug delivery
KW  - human excised skin
KW  - Jurkat cells
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-473270
SN  - 1866-8372
IS  - 1339
ER  - 
TY  - JOUR
A1  - Schoenauer, Roman
A1  - Larpin, Yu
A1  - Babiychuk, Eduard B.
A1  - Drucker, Patrick
A1  - Babiychuk, Viktoriia S.
A1  - Avota, Elita
A1  - Schneider-Schaulies, Sibylle
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Koffel, Rene
A1  - Draeger, Annette
T1  - Down-regulation of acid sphingomyelinase and neutral sphingomyelinase-2 inversely determines the cellular resistance to plasmalemmal injury by pore-forming toxins
JF  - The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology
N2  - Bacterial pore-forming toxins compromise plasmalemmal integrity, leading to Ca2+ influx, leakage of the cytoplasm, and cell death. Such lesions can be repaired by microvesicular shedding or by the endocytic uptake of the injured membrane sites. Cells have at their disposal an entire toolbox of repair proteins for the identification and elimination of membrane lesions. Sphingomyelinases catalyze the breakdown of sphingomyelin into ceramide and phosphocholine. Sphingomyelin is predominantly localized in the outer leaflet, where it is hydrolyzed by acid sphingomyelinase (ASM) after lysosomal fusion with the plasma membrane. The magnesium-dependent neutral sphingomyelinase (NSM)-2 is found at the inner leaflet of the plasmalemma. Because either sphingomyelinase has been ascribed a role in the cellular stress response, we investigated their role in plasma membrane repair and cellular survival after treatment with the pore-forming toxins listeriolysin O (LLO) or pneumolysin (PLY). Jurkat T cells, in which ASM or NSM-2 was down-regulated [ASM knockdown (KD) or NSM-2 KD cells], showed inverse reactions to toxin-induced membrane damage: ASM KD cells displayed reduced toxin resistance, decreased viability, and defects in membrane repair. In contrast, the down-regulation of NSM-2 led to an increase in viability and enhanced plasmalemmal repair. Yet, in addition to the increased plasmalemmal repair, the enhanced toxin resistance of NSM-2 KD cells also appeared to be dependent on the activation of p38/MAPK, which was constitutively activated, whereas in ASM KD cells, the p38/MAPK activation was constitutively blunted.Schoenauer, R., Larpin, Y., Babiychuk, E. B., Drucker, P., Babiychuk, V. S., Avota, E., Schneider-Schaulies, S., Schumacher, F., Kleuser, B., Koffel, R., Draeger, A. Down-regulation of acid sphingomyelinase and neutral sphingomyelinase-2 inversely determines the cellular resistance to plasmalemmal injury by pore-forming toxins.
KW  - membrane repair
KW  - blebbing
KW  - calcium
KW  - bacterial toxins
KW  - annexins
Y1  - 2018
U6  - https://doi.org/10.1096/fj.201800033R
SN  - 0892-6638
SN  - 1530-6860
VL  - 33
IS  - 1
SP  - 275
EP  - 285
PB  - Federation of American Societies for Experimental Biology
CY  - Bethesda
ER  - 
TY  - JOUR
A1  - Solger, Franziska
A1  - Kunz, Tobias C.
A1  - Fink, Julian
A1  - Paprotka, Kerstin
A1  - Pfister, Pauline
A1  - Hagen, Franziska
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Seibel, Jürgen
A1  - Rudel, Thomas
T1  - A role of sphingosine in the intracellular survival of Neisseria gonorrhoeae
JF  - Frontiers in Cellular and Infection Microbiology
N2  - Obligate human pathogenic Neisseria gonorrhoeae are the second most frequent bacterial cause of sexually transmitted diseases. These bacteria invade different mucosal tissues and occasionally disseminate into the bloodstream. Invasion into epithelial cells requires the activation of host cell receptors by the formation of ceramide-rich platforms. Here, we investigated the role of sphingosine in the invasion and intracellular survival of gonococci. Sphingosine exhibited an anti-gonococcal activity in vitro. We used specific sphingosine analogs and click chemistry to visualize sphingosine in infected cells. Sphingosine localized to the membrane of intracellular gonococci. Inhibitor studies and the application of a sphingosine derivative indicated that increased sphingosine levels reduced the intracellular survival of gonococci. We demonstrate here, that sphingosine can target intracellular bacteria and may therefore exert a direct bactericidal effect inside cells.
KW  - Neisseria gonorrhoeae
KW  - sphingosine
KW  - sphingolipids
KW  - sphingosine kinases
KW  - invasion
KW  - survival
KW  - click chemistry
Y1  - 2020
U6  - https://doi.org/10.3389/fcimb.2020.00215
SN  - 2235-2988
VL  - 10
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - GEN
A1  - Beckmann, Nadine
A1  - Becker, Katrin Anne
A1  - Kadow, Stephanie
A1  - Schumacher, Fabian
A1  - Kramer, Melanie
A1  - Kühn, Claudine
A1  - Schulz-Schaeffer, Walter J.
A1  - Edwards, Michael J.
A1  - Kleuser, Burkhard
A1  - Gulbins, Erich
A1  - Carpinteiro, Alexander
T1  - Acid sphingomyelinase deficiency ameliorates Farber disease
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can’t achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1087 
KW  - Farber disease
KW  - lysosomal storage disorders
KW  - acid ceramidase
KW  - acid sphingomyelinase
KW  - amitriptyline
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-441282
SN  - 1866-8372
IS  - 1087
ER  - 
TY  - JOUR
A1  - Derakhshani, Shaghayegh
A1  - Kurz, Andreas
A1  - Japtok, Lukasz
A1  - Schumacher, Fabian
A1  - Pilgram, Lisa
A1  - Steinke, Maria
A1  - Kleuser, Burkhard
A1  - Sauer, Markus
A1  - Schneider-Schaulies, Sibylle
A1  - Avota, Elita
T1  - Measles Virus Infection Fosters Dendritic Cell Motility in a 3D Environment to Enhance Transmission to Target Cells in the Respiratory Epithelium
JF  - Frontiers in immunology
N2  - Transmission of measles virus (MV) from dendritic to airway epithelial cells is considered as crucial to viral spread late in infection. Therefore, pathways and effectors governing this process are promising targets for intervention. To identify these, we established a 3D respiratory tract model where MV transmission by infected dendritic cells (DCs) relied on the presence of nectin-4 on H358 lung epithelial cells. Access to recipient cells is an important prerequisite for transmission, and we therefore analyzed migration of MV-exposed DC cultures within the model. Surprisingly, enhanced motility toward the epithelial layer was observed for MV-infected DCs as compared to their uninfected siblings. This occurred independently of factors released from H358 cells indicating that MV infection triggered cytoskeletal remodeling associated with DC polarization enforced velocity. Accordingly, the latter was also observed for MV-infected DCs in collagen matrices and was particularly sensitive to ROCK inhibition indicating infected DCs preferentially employed the amoeboid migration mode. This was also implicated by loss of podosomes and reduced filopodial activity both of which were retained in MV-exposed uninfected DCs. Evidently, sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as produced in response to virus-infection in DCs contributed to enhanced velocity because this was abrogated upon inhibition of sphingosine kinase activity. These findings indicate that MV infection promotes a push-and-squeeze fast amoeboid migration mode via the SphK/S1P system characterized by loss of filopodia and podosome dissolution. Consequently, this enables rapid trafficking of virus toward epithelial cells during viral exit.
KW  - dendritic cell
KW  - cell migration
KW  - measles virus
KW  - 3D tissue model
KW  - sphingosine-1-phosphate
Y1  - 2019
U6  - https://doi.org/10.3389/fimmu.2019.01294
SN  - 1664-3224
VL  - 10
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Meiners, Jana
A1  - Palmieri, Vittoria
A1  - Klopfleisch, Robert
A1  - Ebel, Jana-Fabienne
A1  - Japtok, Lukasz
A1  - Schumacher, Fabian
A1  - Yusuf, Ayan Mohamud
A1  - Becker, Katrin Anne
A1  - Zöller, Julia
A1  - Hose, Matthias
A1  - Kleuser, Burkhard
A1  - Hermann, Dirk Matthias
A1  - Kolesnick, Richard N.
A1  - Buer, Jan
A1  - Hansen, Wiebke
A1  - Westendorf, Astrid M.
T1  - Intestinal acid sphingomyelinase protects from severe Pathogen-Driven Colitis
JF  - Frontiers in immunology
N2  - Inflammatory diseases of the gastrointestinal tract are emerging as a global problem with increased evidence and prevalence in numerous countries. A dysregulated sphingolipid metabolism occurs in patients with ulcerative colitis and is discussed to contribute to its pathogenesis. In the present study, we determined the impact of acid sphingomyelinase (Asm), which catalyzes the hydrolysis of sphingomyelin to ceramide, on the course of Citrobacter (C.) rodentium-driven colitis. C. rodentium is an enteric pathogen and induces colonic inflammation very similar to the pathology in patients with ulcerative colitis. We found that mice with Asm deficiency or Asm inhibition were strongly susceptible to C. rodentium infection. These mice showed increased levels of C. rodentium in the feces and were prone to bacterial spreading to the systemic organs. In addition, mice lacking Asm activity showed an uncontrolled inflammatory T(h)1 and T(h)17 response, which was accompanied by a stronger colonic pathology compared to infected wild type mice. These findings identified Asm as an essential regulator of mucosal immunity to the enteric pathogen C. rodentium.
KW  - Citrobacter rodentium
KW  - colitis
KW  - acid sphingomyelinase
KW  - amitriptyline
KW  - T(h)1
KW  - T(h)17
Y1  - 2019
U6  - https://doi.org/10.3389/fimmu.2019.01386
SN  - 1664-3224
VL  - 10
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Hausmann, Christian
A1  - Zoschke, Christian
A1  - Wolff, Christopher
A1  - Darvin, Maxim E.
A1  - Sochorova, Michaela
A1  - Kovacik, Andrej
A1  - Wanjiku, Barbara
A1  - Schumacher, Fabian
A1  - Tigges, Julia
A1  - Kleuser, Burkhard
A1  - Lademann, Juergen
A1  - Fritsche, Ellen
A1  - Vavrova, Katerina
A1  - Ma, Nan
A1  - Schaefer-Korting, Monika
T1  - Fibroblast origin shapes tissue homeostasis, epidermal differentiation, and drug uptake
JF  - Scientific reports
N2  - Preclinical studies frequently lack predictive value for human conditions. Human cell-based disease models that reflect patient heterogeneity may reduce the high failure rates of preclinical research. Herein, we investigated the impact of primary cell age and body region on skin homeostasis, epidermal differentiation, and drug uptake. Fibroblasts derived from the breast skin of female 20- to 30-yearolds or 60- to 70-year-olds and fibroblasts from juvenile foreskin (<10 years old) were compared in cell monolayers and in reconstructed human skin (RHS). RHS containing aged fibroblasts differed from its juvenile and adult counterparts, especially in terms of the dermal extracellular matrix composition and interleukin-6 levels. The site from which the fibroblasts were derived appeared to alter fibroblast-keratinocyte crosstalk by affecting, among other things, the levels of granulocyte-macrophage colony-stimulating factor. Consequently, the epidermal expression of filaggrin and e-cadherin was increased in RHS containing breast skin fibroblasts, as were lipid levels in the stratum corneum. In conclusion, the region of the body from which fibroblasts are derived appears to affect the epidermal differentiation of RHS, while the age of the fibroblast donors determines the expression of proteins involved in wound healing. Emulating patient heterogeneity in preclinical studies might improve the treatment of age-related skin conditions.
Y1  - 2019
U6  - https://doi.org/10.1038/s41598-019-39770-6
SN  - 2045-2322
VL  - 9
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - GEN
A1  - Wigger, Dominik
A1  - Gulbins, Erich
A1  - Kleuser, Burkhard
A1  - Schumacher, Fabian
T1  - Monitoring the Sphingolipid de novo Synthesis by Stable-Isotope Labeling and Liquid Chromatography-Mass Spectrometry
T2  - Postprints der Universität Potsdam Mathematisch-Naturwissenschaftliche Reihe
N2  - Sphingolipids are a class of lipids that share a sphingoid base backbone. They exert various effects in eukaryotes, ranging from structural roles in plasma membranes to cellular signaling. De novo sphingolipid synthesis takes place in the endoplasmic reticulum (ER), where the condensation of the activated C₁₆ fatty acid palmitoyl-CoA and the amino acid L-serine is catalyzed by serine palmitoyltransferase (SPT). The product, 3-ketosphinganine, is then converted into more complex sphingolipids by additional ER-bound enzymes, resulting in the formation of ceramides. Since sphingolipid homeostasis is crucial to numerous cellular functions, improved assessment of sphingolipid metabolism will be key to better understanding several human diseases. To date, no assay exists capable of monitoring de novo synthesis sphingolipid in its entirety. Here, we have established a cell-free assay utilizing rat liver microsomes containing all the enzymes necessary for bottom-up synthesis of ceramides. Following lipid extraction, we were able to track the different intermediates of the sphingolipid metabolism pathway, namely 3-ketosphinganine, sphinganine, dihydroceramide, and ceramide. This was achieved by chromatographic separation of sphingolipid metabolites followed by detection of their accurate mass and characteristic fragmentations through high-resolution mass spectrometry and tandem-mass spectrometry. We were able to distinguish, unequivocally, between de novo synthesized sphingolipids and intrinsic species, inevitably present in the microsome preparations, through the addition of stable isotope-labeled palmitate-d₃ and L-serine-d₃. To the best of our knowledge, this is the first demonstration of a method monitoring the entirety of ER-associated sphingolipid biosynthesis. Proof-of-concept data was provided by modulating the levels of supplied cofactors (e.g., NADPH) or the addition of specific enzyme inhibitors (e.g., fumonisin B₁). The presented microsomal assay may serve as a useful tool for monitoring alterations in sphingolipid de novo synthesis in cells or tissues. Additionally, our methodology may be used for metabolism studies of atypical substrates – naturally occurring or chemically tailored – as well as novel inhibitors of enzymes involved in sphingolipid de novo synthesis.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 800 
KW  - sphingolipid de novo synthesis
KW  - serine palmitoyltransferase
KW  - mass spectrometry
KW  - stable-isotope labeling
KW  - ceramides
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-441158
SN  - 1866-8372
IS  - 800
ER  - 
TY  - JOUR
A1  - Beckmann, Nadine
A1  - Becker, Katrin Anne
A1  - Kadow, Stephanie
A1  - Schumacher, Fabian
A1  - Kramer, Melanie
A1  - Kuehn, Claudine
A1  - Schulz-Schaeffer, Walter J.
A1  - Edwards, Michael J.
A1  - Kleuser, Burkhard
A1  - Gulbins, Erich
A1  - Carpinteiro, Alexander
T1  - Acid Sphingomyelinase Deficiency Ameliorates Farber Disease
JF  - International journal of molecular sciences
N2  - Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can’t achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients.
KW  - Farber disease
KW  - lysosomal storage disorders
KW  - acid ceramidase
KW  - acid sphingomyelinase
KW  - amitriptyline
Y1  - 2019
U6  - https://doi.org/10.3390/ijms20246253
SN  - 1422-0067
VL  - 20
IS  - 24
PB  - MDPI
CY  - Basel
ER  -