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Cell membrane cholesterol and lipid rafts (membrane microdomains) are specialized, dynamic regions of the plasma membrane enriched in cholesterol, sphingolipids, and specific proteins (Sezgin et al., 2017, Nature Reviews Molecular Cell Biology). These microdomains act as organizing centers or signaling hubs that facilitate the assembly of signaling complexes, regulate membrane fluidity, and manage protein trafficking and endocytosis (Simons & Sampaio, 2011, Cold Spring Harbor Perspectives in Biology). In various diseases, lipid rafts are hijacked; for instance, they serve as entry points for pathogens like HIV and SARS-CoV-2, and they harbor overactive growth factor receptors in cancer cells (Varshney et al., 2016, Frontiers in Cell and Developmental Biology). Therapeutic strategies targeting these domains often involve the depletion or sequestration of cholesterol to disrupt raft integrity, thereby inhibiting pathological signaling or viral entry (Mollinedo & Gajate, 2015, Advances in Biological Regulation). Drugs such as cyclodextrins and polyene antibiotics interact directly with membrane cholesterol to alter these structures (Sonnino & Prinetti, 2013, FEBS Letters). However, because cholesterol is a fundamental component of all mammalian cell membranes, achieving selectivity and avoiding systemic toxicity, such as ototoxicity or hemolysis, remains a significant clinical challenge (Zidovetzki & Levitan, 2007, Biochimica et Biophysica Acta).
Cholesterol depletion, sequestration, or disruption of lipid raft integrity to modulate signaling pathways and inhibit pathogen entry (Varshney et al., 2016, Frontiers in Cell and Developmental Biology).
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