Molecular Mind Games: The Medicinal Action of Cyclodextrins in Neurodegenerative Diseases

Abstract

Cyclodextrins are often used as molecular carriers for small active ingredients in medicine. Recently, the intrinsic medicinal activity of some of these compounds has been under investigation, mainly related to their ability to interfere with cholesterol and, therefore, prevent and treat cholesterol-related diseases such as cardiovascular disease and neuronal diseases arising from altered cholesterol and lipid metabolism. One of the most promising compounds within the cyclodextrin family is 2-hydroxypropyl-β-cyclodextrin (HPβCD), owing to its superior biocompatibility profile. This work presents the most recent advances in the research and clinical use of HPβCD against Niemann–Pick disease, a congenital condition involving cholesterol accumulation inside lysosomes in brain cells, Alzheimer’s and Parkinson’s. HPβCD plays a complex role in each of these ailments, going beyond the mere sequestering of cholesterol molecules and involving an overall regulation of protein expression that helps restore the normal functioning of the organism.

Exploring the role of cyclodextrins as a cholesterol scavenger: a molecular dynamics investigation of conformational changes and thermodynamics

“…The mechanisms underlying these interactions are still being investigated, but the potential applications of CDs as cholesterol-lowering agents have been demonstrated in preclinical and clinical studies. The use of CDs as cholesterol-lowering agents has the potential to provide a safe and effective alternative to traditional cholesterol-lowering drugs 15 , 16 . The interaction between cholesterol and CDs is primarily driven by the hydrophobic effect, which arises from the tendency of nonpolar molecules to aggregate in aqueous solutions.…”

Cholesterol Modulation Attenuates the AD-Like Phenotype Induced by Herpes Simplex Virus Type 1 Infection

“…Cyclodextrins (CDs) are commonly used compounds to rapidly deplete cells of cholesterol. They have been tested for clinical purposes in certain Lysosome Storage Disorders (LSDs), such as NPC, and certain neuro-degenerative diseases (reviewed in [36]). NPC is a severe congenital disease caused by mutations in the NPC1 and NPC2 genes, which are involved in cholesterol transport within the lysosome [37].…”

Cholesterol Modulation Attenuates the AD-like Phenotype Induced by Herpes Simplex Virus Type 1 Infection

“…For instance, MβCD treatment of HSV-1 particles inhibited viral entry, indicating that virion envelope cholesterol is critical for membrane fusion of viral particles [37]. In addition, CDs have been tested for clinical purposes in certain lysosome storage disorders (LSDs), such as NPC, and certain neurodegenerative diseases (reviewed in [38]). NPC is a severe congenital disease caused by mutations in the NPC1 and NPC2 genes, which are involved in cholesterol transport within the lysosome [39].…”