Article
Biochemistry & Molecular Biology
Mazen Aseeri, Jose Luis Abad, Antonio Delgado, Gemma Fabrias, Gemma Triola, Josefina Casas
Summary: Ceramide plays a crucial role in regulating cellular senescence and apoptosis. Acid ceramidase (AC) reduces Ceramide levels, which is abnormally expressed in various cancers. However, the lack of suitable screening formats has hindered AC inhibitor discovery. In this study, a fluorogenic assay was adapted to a 384-well plate format, overcoming this limitation. The optimized platform successfully screened a library of 4100 compounds and identified several hits with potency ranges of 2-25 μM, belonging to different chemical classes. These inhibitors showed selectivity for neutral ceramidase and retained activity in cells, serving as a basis for further chemical optimization.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Yuan Jiang, Xingxuan He, Calogera M. Simonaro, Bin Yi, Edward H. Schuchman
Summary: The study demonstrates that recombinant acid ceramidase has therapeutic potential in hepatic ischemia reperfusion injury in mice, reducing damage and decreasing oxidative stress and inflammation. Changes in sphingolipid metabolism play a crucial role in the injury, and administration of acid ceramidase can alter sphingolipid levels and other pathologic changes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Plant Sciences
Li-Qun Huang, Ping-Ping Li, Jian Yin, Yong-Kang Li, Ding-Kang Chen, He-Nan Bao, Rui-Yuan Fan, Hao-Zhuo Liu, Nan Yao
Summary: Plant sphingolipids play important roles in membrane composition and defense responses. This study reveals that feeding by Spodoptera exigua affects sphingolipid metabolism in Arabidopsis, leading to increased levels of certain sphingolipids. The accumulation of these sphingolipids is dependent on the jasmonate signaling pathway. Loss of the alkaline ceramidase ACER enhances plant resistance to S. exigua and improves response to mechanical wounding and exogenous jasmonate, indicating the involvement of ACER in jasmonate-mediated plant defense and growth.
JOURNAL OF EXPERIMENTAL BOTANY
(2022)
Article
Biochemistry & Molecular Biology
Albena Momchilova, Roumen Pankov, Alexander Alexandrov, Tania Markovska, Stefan Pankov, Plamen Krastev, Galya Staneva, Evgenia Vassileva, Nikolai Krastev, Adriana Pinkas
Summary: This study analyzed the lipid composition and sphingolipid-catabolizing enzymes in the blood of multiple sclerosis (MS) patients and found changes in the levels of sphingomyelin and its products. The activity of acid sphingomyelinase and alkaline ceramidase also showed alterations. Additionally, differences in the ratios of saturated, unsaturated, and polyunsaturated fatty acids were observed, which could potentially serve as markers for distinguishing MS patients from healthy controls. The application of lipid analysis in medical practice could contribute to more precise diagnosis, analysis of disease progression, and evaluation of therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Lindsey T. Lelieveld, Sophie Gerhardt, Saskia Maas, Kimberley C. Zwiers, Claire de Wit, Ernst H. Beijk, Maria J. Ferraz, Marta Artola, Annemarie H. Meijer, Christian Tudorache, Daniela Salvatori, Rolf G. Boot, Johannes M. F. G. Aerts
Summary: In Gaucher disease, excessive GlcSph has little impact on (neuro)inflammation or GlcCer-laden macrophages, but rather seems harmful to th1-positive dopaminergic neurons.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Michele Lai, Veronica La Rocca, Rachele Amato, Giulia Freer, Mario Costa, Pietro Giorgio Spezia, Paola Quaranta, Giuseppe Lombardo, Daniele Piomelli, Mauro Pistello
Summary: Cutaneous melanoma is often resistant to therapy due to its high plasticity and ability to metabolize chemotherapeutic drugs. AC-null melanoma cells exhibit impaired autophagy but increased mitochondrial membrane potential, leading to higher apoptosis rates in nutrient-deprived conditions compared to wild-type cells. AC transfection can restore viability in AC-null cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Helen Shiphrah Vethakanraj, Niveditha Chandrasekaran, Ashok Kumar Sekar
Summary: AC plays a critical role in cancer progression, with its upregulation leading to increased cell proliferation, metastasis, chemoresistance, and radioresistance. Gene silencing and pharmacological inhibition of AC can enhance sensitivity of resistant cells to therapy, thereby promoting cell death.
CURRENT CANCER DRUG TARGETS
(2021)
Article
Pharmacology & Pharmacy
Nuseibah AL Qtaish, Idoia Gallego, Ilia Villate- Beitia, Myriam Sainz-Ramos, Gema Martinez-Navarrete, Cristina Soto-Sanchez, Eduardo Fernandez, Patricia Galvez-Martin, Tania B. Lopez-Mendez, Gustavo Puras, Jose Luis Pedraz
Summary: Compared to niosomes, niosphingosomes and their corresponding complexes showed decreased particle size and increased superficial charge. Cell viability and transfection efficiency increased when cells were exposed to niosphingoplexes, although there were no significant differences in cellular uptake. Niosphingoplexes exhibited decreased endocytosis via caveolae, higher co-localization with the lysosomal compartment, and enhanced endosomal escape properties.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2021)
Review
Biochemistry & Molecular Biology
Yasharah Raza, Jane Atallah, Chiara Luberto
Summary: Dysregulation of sphingolipid metabolism plays a complex role in hematological malignancies, contributing to the design of combinatorial therapeutic regimens and reducing resistance to standard therapies. Inhibitors targeting specific nodes of the sphingolipid pathway significantly decrease leukemic cell survival. The recent advances in this field focus on the latter part of the last decade.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Respiratory System
Michael G. Katz, Yoav Hadas, Adam Vincek, Lina Freage-Kahn, Nataly Shtraizent, Jeko M. Madjarov, Peter Pastuszko, Efrat Eliyahu
Summary: Gene delivery of acid ceramidase ameliorated vascular remodeling and right ventricular dysfunction in pulmonary hypertension. It decreased levels of pro-inflammatory factors, interleukins, and senescence markers in the PH model animals.
RESPIRATORY RESEARCH
(2023)
Article
Multidisciplinary Sciences
Michele Lai, Rachele Amato, Veronica La Rocca, Mesut Bilgin, Giulia Freer, Piergiorgio Spezia, Paola Quaranta, Daniele Piomelli, Mauro Pistello
Summary: The study shows that acid ceramidase plays a crucial role in melanoma cells' response to doxorubicin. Blocking AC reduces cell resistance to the drug and pushes cells towards apoptosis.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Hanmeng Zhang, Murtaza S. Nagree, Haoyuan Liu, Xiaoqing Pan, Jeffrey A. Medin, Daniel M. Lipinski
Summary: rAAV-mediated ASAH1 over-expression can reduce retinopathy in Farber disease mice, while unexpectedly causing retinal issues in normal mice that resemble Farber disease phenotype.
Article
Cell Biology
Ruijuan Xu, Paul Antwi Boasiako, Cungui Mao
Summary: Ceramidases are enzymes that catalyze the hydrolysis of ceramide compounds into sphingosine, dihydrosphingosine, and phytosphingosine, along with a free fatty acid. Alkaline ceramidases, a subtype of ceramidases, play important roles in regulating sphingolipid metabolism and biological processes, with unique substrate specificity. The ACER family, consisting of various alkaline ceramidase genes identified across species, constitutes a large protein family with potential diverse functions.
CELLULAR SIGNALLING
(2021)
Review
Chemistry, Medicinal
Mohammad Mohiminul Islam, Shama P. Mirza
Summary: This article summarizes the chemistry, pharmacokinetics, and pharmacology of carmofur, an antineoplastic drug used for the treatment of colorectal cancer. It also discusses its potential applications in other diseases and its antifungal and antimicrobial properties.
DRUG DEVELOPMENT RESEARCH
(2022)
Article
Cell Biology
Cyntanna C. Hawkins, Amber B. Jones, Emily R. Gordon, Sarah E. Williford, Yuvika Harsh, Julia K. Ziebro, Catherine J. Landis, G. C. Sajina, David K. Crossman, Sara J. Cooper, Sasanka Ramanadham, Ninh Doan, Anita B. Hjelmeland
Summary: In this study, the researchers found that acid ceramidase (ASAH1) is highly expressed in GBM and is associated with migration-related genes. Through shRNA knockdown and carmofur inhibition, they demonstrated the role of ASAH1 in GBM migration. Inhibition of ASAH1 using carmofur may be a potential clinically relevant treatment for GBM.
Article
Neurosciences
Jean- Pierre Obeid, Youssef H. Zeidan, Nawal Zafar, Jimmy El Hokayem
MOLECULAR NEUROBIOLOGY
(2018)
Article
Oncology
Youssef H. Zeidan, Joyce G. Habib, Lieveke Ameye, Marianne Paesmans, Evandro de Azambuja, Richard D. Gelber, Ian Campbell, Bo Nordenskjold, Jorge Gutierez, Michael Anderson, Ana Lluch, Michael Gnant, Aron Goldhirsch, Angelo Di Leo, David J. Joseph, John Crown, Martine Piccart-Gebhart, Prudence A. Francis
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2018)
Editorial Material
Oncology
Youssef H. Zeidan, Joyce G. Habib, Evandro de Azambuja, Ian Campbell, Michael Andersson, Ana Lluch, Angelo Di Leo, Prudence A. Francis
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2018)
Article
Endocrinology & Metabolism
Shaheen Alanee, Ahmed El-Zawahry, Danuta Dynda, Ali Dabaja, Kevin McVary, Mallory Karr, Andrea Braundmeier-Fleming
Article
Oncology
Shaheen Alanee, Ahmed El-Zawahry, Danuta Dynda, Kevin McVary, Mallory Karr, Andrea Braundmeier-Fleming
PROSTATE CANCER AND PROSTATIC DISEASES
(2019)
Article
Urology & Nephrology
Ahmed El-Zawahry
CURRENT UROLOGY REPORTS
(2019)
Editorial Material
Obstetrics & Gynecology
Ahmed El-Zawahry, Diaa E. E. Rizk
INTERNATIONAL UROGYNECOLOGY JOURNAL
(2020)
Article
Urology & Nephrology
Bradley Holland, Mallory Karr, Kristin Delfino, Danuta Dynda, Ahmed El-Zawahry, Andrea Braundmeier-Fleming, Kevin McVary, Shaheen Alanee
Article
Urology & Nephrology
Robert A. Petrossian, Danuta Dynda, Kristin Delfino, Ahmed El-Zawahry, Kevin T. McVary
CANADIAN JOURNAL OF UROLOGY
(2020)
Article
Urology & Nephrology
Omar Dawood, Seena Tabibi, Julia Fiuk, Neil Patel, Ahmed El-Zawahry
Meeting Abstract
Oncology
Shaheen Alanee, Ahmed El Zawahry, Sherjeel Sana, Kevin McVary, Kathy Robinson, Krishna A. Rao
Meeting Abstract
Urology & Nephrology
Shaheen Alanee, Ahmed El-Zawahry, Kevin McVary, Mustafa Deebajah, Sherjeel Sana, Kathy Robinson, Krishna Rao
JOURNAL OF UROLOGY
(2019)
Meeting Abstract
Urology & Nephrology
Shaheen Alanee, Bradley Holland, Kristin Delfino, Danuta Dynda, Ahmed El-Zawahry, Andrea Braundmeier, Kevin McVary
JOURNAL OF UROLOGY
(2019)
Meeting Abstract
Urology & Nephrology
Shaheen Alanee, Ahmed El-Zawahry, Mallory Karr, Mustafa Deebajah, Ali Dabaja, Danuta Dynda, Kevin Mcvary, Andrea Braundmeier-Fleming
JOURNAL OF UROLOGY
(2018)
Meeting Abstract
Urology & Nephrology
Shaheen Alanee, Ahmed El-Zawahry, Mallory Karr, Mustafa Deebajah, Ali Dabaja, Danuta Dynda, Kevin Mcvary, Andrea Braundmeier-Fleming
JOURNAL OF UROLOGY
(2018)