BCM-95® (CURCUGREEN®), 20 Mar 2021
Published on : Human Molecular Genetics, Volume 24, Issue 15, 1 August 2015, Pages 4198–4211, https://doi.org/10.1093/hmg/ddv153 Published: 29 April 2015
Massimo Tatti, Marialetizia Motta, Susanna Scarpa, Sabrina Di Bartolomeo, Valentina Cianfanelli, Marco Tartaglia, Rosa Salvioli
Saposin (Sap) C deficiency is a rare variant form of Gaucher disease caused by impaired Sap C expression or accelerated degradation, and associated with accumulation of glucosylceramide and other lipids in the endo/lysosomal compartment. No effective therapies are currently available for the treatment of Sap C deficiency. We previously reported that a reduced amount and enzymatic activity of cathepsin (Cath) B and Cath D, and defective autophagy occur in Sap C-deficient fibroblasts. Here, we explored the use of two compounds, BCM-95, a curcumin derivative, and (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD), to improve lysosomal function of Sap C-deficient fibroblasts. Immunofluorescence and biochemical studies documented that each compound promotes an increase of the expression levels and activities of Cath B and Cath D, and efficient clearance of cholesterol (Chol) and ceramide (Cer) in lysosomes. We provide evidence that BCM-95 and HP-β-CD enhance lysosomal function promoting autophagic clearance capacity and lysosome reformation. Our findings suggest a novel pharmacological approach to Sap C deficiency directed to treat major secondary pathological aspects in this disorder.
© The Author 2015. Published by Oxford University Press. All rights reserved.