Hormonal modulation of cholesterol: experimental evidence and possible translational impact

Abstract

Alzheimer's disease (AD) is still an incurable condition. There is in vitro evidence that estrogens exert neuroprotective effects; however, their role in the treatment of AD is still controversial. Approximately 10 years ago, a new gene, named seladin-1 (for selective AD indicator-1), was identified and found to be downregulated in brain regions affected by AD. Seladin-1 has neuroprotective properties, which have been associated, at least in part, with its anti-apoptotic activity. Estrogens stimulate the expression of the seladin-1 gene. Seladin-1 also has enzymatic activity (3-β-hydroxysterol Δ-24-reductase), 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 focuses on the relationship between estrogens (and IGF-1, another hormone with neuroprotective properties), cholesterol and seladin-1.

Keywords::

• Alzheimer's disease
• cholesterol
• estrogens
• IGF-1
• neurodegeneration
• seladin-1

Acknowledgements

This article is dedicated to the memory of Mario Serio, who tragically passed away a year ago. He was and will continue to be an extraordinary source of inspiration for all of us.

Financial & competing interests disclosure

The experimental work performed by the authors and reported in this review was supported by grants from Ente Cassa di Risparmio di Firenze and from Regione Toscana ‘Bando Salute 2009’. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.