Interactions between cyclodextrins and cellular components: Towards greener medical applications?

Leclercq, Loïc

AD is a chronic neurodegenerative disease which represents 60% to 70% of cases of dementia. This disease is characterized by the formation of amyloid plaques in the brain and is often associated to the cerebral accumulation of amyloidogenic peptides (Aβ42). This production is mediated by two neuronal enzymes (β-and γ-secretase) which can be inhibited by methylated β-CDs via cholesterol depletion [137] . Additionally, Yao and co-workers demonstrated that HP-β-CD reduces cell membrane cholesterol accumulation in N2a cells overexpressing Swedish mutant APP (SwN2a) [138] . Moreover, this CD dramatically lowered the levels of Aβ42 in cells as well as the amyloid plaque deposition by reduction of APP protein β cleavage and by up-regulation of the gene expression involved in cholesterol transport. In cell models, this CD also improved clearance mechanisms.