Hormonal modulation of cholesterol: experimental evidence and possible translational impact

Alzheimer’s disease (AD) is still an incurable condition. There is in vitro evidence that that estrogens exert neuroprotective effects; however, their role in the treatment of AD is still controversial. About 10 years ago, a new gene, named seladin-1 (for Selective Alzheimer’s Disease indicator-1), was identified and found to be down regulated in brain regions involved in AD. Seladin-1 has neuroprotective properties, that have been associated, at least in part, to its anti-apoptotic activity. Estrogens stimulate the expression of the seladin-1 gene. Seladin-1 has also enzymatic activity [3-β-hydroxysterol delta-24-reductase, (DHCR24)], which is involved in the synthesis of cholesterol from desmosterol. The amount of membrane cholesterol appears to play an important role in conferring protection to brain cells. This review will be focused on the relationship that occurs between estrogens (and IGF-1, another hormone with neuroprotective properties), cholesterol and seladin-1.