Heegon Kim
SCIENCE
Pathological intracellular cholesterol accumulation disrupts cellular homeostasis across multiple diseases, creating a therapeutic opportunity to restore cholesterol balance at the cellular level.
Cholesterol: Essential, Yet Toxic in Excess
Cholesterol plays essential roles in the human body, serving as a fundamental component of cell membranes and a precursor for hormones, vitamin D, and other bioactive molecules. However, when cholesterol homeostasis is disrupted, cholesterol can accumulate excessively within cells and cause cellular stress and toxicity. Pathological intracellular cholesterol accumulation is increasingly recognized as an important contributor to the pathophysiology of multiple age-related and metabolic diseases, including atherosclerosis, neurodegenerative disorders,and chronic kidney disease.
Cyclodextrin as Cholesterol Modulators
Cyclodextrins are ring-shaped molecules capable of forming inclusion complexes with cholesterol through their hydrophobic cavity. By mobilizing pathologically accumulated cholesterol and promoting its redistribution or removal, cyclodextrins help restore cholesterol homeostasis and reduce cholesterol-induced cellular stress. This mode of action provides a distinct therapeutic strategy for diseases associated with pathological intracellular cholesterol accumulation.
Beyond Lowering Blood Cholesterol
Statins and other lipid-lowering therapies primarily reduce circulating LDL cholesterol. However, they do not directly target cholesterol that has already accumulated within cells, including cholesterol sequestered in lysosomes, where it may contribute to crystal formation, inflammatory signaling, and cellular dysfunction. By acting directly on this intracellular cholesterol pool, cyclodextrins offer a mechanism complementary to existing lipid-lowering therapies, with the potential to reshape the treatment landscape for cholesterol-associated diseases.