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Sphingomyelin Inhibits Hydrolytic Activity of Heterodimeric PLA2 in Model Myelin Membranes: Pharmacological Relevance

Authors: Anwaar S. Chaudary,Yanglin Guo,Yuri N. Utkin,Maryam Barancheshmeh,Ruben K. Dagda,Edward S. Gasanoff
Publisher: Springer Science and Business Media LLC
Publish date: 2024-10-22
ISSN: 0022-2631,1432-1424 DOI: 10.1007/s00232-024-00327-y
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This paper presents a fascinating exploration of sphingomyelin’s inhibitory effects on HDP-2, with potential implications for neurodegenerative disease treatments. One intriguing takeaway was how sphingomyelin alters lipid dynamics within the model myelin membrane. Could this inhibitory mechanism extend beyond hydrolytic activity to modulate other enzymatic pathways associated with myelin lipid turnover?

I also noticed the reliance on molecular docking for structural insights. While the data convincingly supports sphingomyelin’s binding, how do these findings compare to potential results in live-cell systems or animal models? Such a comparison could offer a more direct link to clinical relevance.

Finally, the study highlights SM’s unique role, but I wonder if other sphingolipids (e.g., ceramides or glycosphingolipids) might exhibit similar or complementary effects. Could this pave the way for a broader lipid-centric therapeutic strategy?

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