Neuroprotective effects of estrogens: the role of cholesterol

Experimental and clinical evidence suggests that estrogens have protective effects in the brain. Nevertheless, their potential role against neurodegenerative diseases, in particular Alzheimer's disease (AD), is still a matter of debate. The identification of the seladin-1 gene (for SELective Alzheimer's Disease INdicator-1), which appeared to be significantly less expressed in brain region affected in AD, opened a new scenario in the field of neuroprotective mechanisms. Seladin-1 was found to have neuroprotective properties through its anti-apoptotic activity. In addition, it was subsequently demonstrated that seladin-1 also has enzymatic activity, because it catalyzes the conversion of desmosterol into cholesterol. Several studies have shown that an appropriate amount of membrane cholesterol plays a pivotal role to protect nerve cells against β-amyloid toxicity in AD and to counteract the synthesis of β-amyloid.