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Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy are two ultra-rare lysosomal storage disorders resulting from loss-of-function mutations in the ASAH1 gene encoding for acid ceramidase (ACDase). ACDase deficiency leads to the intracellular accumulation of ceramides with an inflammatory response in tissues. These two diseases manifest differently but are part of a clinical continuum with variable severity affecting the nervous system and/or peripheral tissues, including the neuromuscular system. To date, no specific or curative treatments are available for patients affected by acid ceramidase deficiency. Here, we summarize the clinical features, enzyme function, mouse models and therapeutic perspectives for these allelic diseases.
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http://dx.doi.org/10.1051/medsci/2024162 | DOI Listing |
J Agric Food Chem
September 2025
Department of Agricultural, Food and Nutritional Sciences, 4-10 Ag/For Building, University of Alberta, Edmonton, Alberta T6G 2P5, Canada.
IRW, an antihypertensive peptide derived from ovotransferrin, has been shown to lower blood pressure in spontaneously hypertensive rats (SHRs) by upregulating angiotensin-converting enzyme 2 (ACE2). ACE2 is cardioprotective and a well-documented inhibitor of apoptosis. This study aims to investigate the anti-apoptotic effects of IRW and its underlying mechanism in SHRs' vasculature.
View Article and Find Full Text PDFSci Transl Med
August 2025
Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, CA 94143, USA.
Tissue fibrosis arises from a critical imbalance between the production and breakdown of extracellular matrix (ECM) components. Whereas current strategies predominantly focus on curbing ECM production, the possibility of promoting ECM degradation to resolve fibrosis remains largely untapped. The role of hepatic stellate cells (HSCs) in ECM degradation is an intriguing area for investigation.
View Article and Find Full Text PDFACS Omega
August 2025
Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143, United States.
Acid ceramidase (aCDase) is an essential enzyme in sphingolipid metabolism and has been linked to various pathological conditions, including cancer and fibrosis. In our previous studies, we observed that inhibiting aCDase with B13 () helped alleviate liver fibrosis in mouse models and in ex vivo human precision-cut liver slices. However, B13 () showed limited potency, prompting us to search for more effective aCDase inhibitors.
View Article and Find Full Text PDFJ Occup Environ Med
August 2025
Hacettepe University, Faculty of Pharmacy, Department of Toxicology, Ankara/Turkey.
Objective: Silicosis is a fibrotic lung disease caused by the inhalation of crystalline silica. This study investigates sphingolipid metabolism in silicosis patients using plasma samples.
Methods: GC-MS-based untargeted metabolomics identified alterations in the sphingolipid pathway, while LC-MS targeted specific ceramide and sphingomyelin species.
JIMD Rep
September 2025
Paediatric Bone Marrow Transplant Unit, Royal Manchester Children's Hospital Manchester University NHS Trust Manchester UK.
Farber's lipogranulomatosis (FL) is an autosomal recessive lipid storage disorder, arising as a consequence of genetic acid ceramidase deficiency. Clinically, it presents as severe arthritis, voice hoarseness, and widespread, painful subcutaneous nodules (SCN). For those without CNS involvement, haematopoietic stem cell transplant provides a viable option for the improvement of both respiratory and musculoskeletal morbidity.
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