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Neuroprotective effects of estrogens: the role of cholesterol

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Abstract

Introduction

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.

Methods and Results

We demonstrated that the expression of seladin-1, as well as the synthesis of cell cholesterol, is stimulated by estrogens in human neuronal precursor cells. Cholesterol enriched cells became more resistant against oxidative stress and β-amyloid toxicity. We thus hypothesized that seladin-1 might be a mediator of the neuroprotective effects of estrogens. Indeed, in cells in which seladin-1 gene expression had been silenced by siRNA the protective effects of estrogens were lost. This finding indicates that seladin-1 is a crucial mediator of the neuroprotective effects of these hormones, at least in our cell model.

Conclusions

In summary, these results establish a new link between estrogens and cholesterol, which is represented by the neuroprotective factor seladin-1.

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Acknowledgments

The studies reported in this review were supported by grants from Ente Cassa di Risparmio di Firenze, from the Regione Toscana-Bando Salute 2009 and from Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN 2009 n. 2009YJTBAZ). I wish to thank my collaborators, in particular Drs. Susanna Benvenuti, Paola Luciani, Cristiana Deledda, Corinna Giuliani and Benedetta Fibbi. Without their constant help I would not have been able to write this review. The prize of the Italian Society of Endocrinology is largely “their prize”. I specially thank my family, my wife Silvana together with Niccolò and Giulia, for having supported me throughout all these years. I have to remember my colleagues at the University of Florence, in particular my mentor, Prof. Mario Serio, who always encouraged my ideas and my work. Finally, I wish to mention Prof. Aldo Pinchera. It is a great honor for me to have received a prize entitled to his memory.

Conflict of interest

I declare that I do not have any conflict of interest related to the submitted manuscript.

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I declare that no humans or animals were used by the author and his collaborators to generate the data reported in this review.

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No Informed consent was necessary for the data reported in this review.

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  1. Endocrine Unit, Department of Experimental and Biomedical Sciences “Mario Serio”, Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies, University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy

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Peri, A. Neuroprotective effects of estrogens: the role of cholesterol. J Endocrinol Invest 39, 11–18 (2016). https://doi.org/10.1007/s40618-015-0332-5

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