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Altered expression of 3-betahydroxysterol delta-24-reductase/selective Alzheimer’s disease indicator-1 gene in Huntington’s disease models

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Abstract

Introduction

3-betahydroxysterol delta-24-reductase (DHCR24), also called selective Alzheimer’s disease indicator-1, is a crucial enzyme in cholesterol biosynthesis with neuroprotective properties that is downregulated in brain areas affected by Alzheimer’s disease.

Aim

In the present study, we investigated modifications of DHCR24 expression in models of Huntington’s disease (HD), a neurodegenerative disorder caused by a polyglutamine expansion in huntingtin (Htt) protein that induces degeneration of cerebral cortex and striatum as well as lateral hypothalamic abnormality.

Methods

Basal expression of DHCR24 and its modulation after oxidative stress were evaluated in rat striatal precursors cells (ST14A) transfected with wild-type (Htt) or mutant Htt (mHtt) and in brain tissue of an HD mouse model (R6/2).

Results

The results showed that DHCR24 transcript levels were decreased in ST14A cells expressing mHtt and in the brain of symptomatic R6/2 mice, but were significantly increased in ST14A cells overexpressing wild-type Htt. In addition, we demonstrated that, in the striatal precursors, the decrease of DHCR24 expression in response to oxidative stress was modified according to the presence of Htt or of its mutant form. Preliminary results indicated a modification of DHCR24 expression in post-mortem brain samples of HD patients.

Conclusions

In conclusion, these results support the hypothesis of a possible role of DHCR24 in HD.

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Abbreviations

DHCR24:

3-betahydroxysterol delta-24-reductase

HD:

Huntington’s disease

AD:

Alzheimer’s disease

Htt:

Huntingtin

mHtt:

Mutant Htt

18S:

Ribosomal 18S subunit

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Acknowledgments

This study was supported by Ministero Istruzione Università e Ricerca (MIUR) (R.M., A.P.), Ente Cassa di Risparmio di Firenze and from Regione Toscana “Bando Salute 2009″, Telethon Foundation (R.M., M.G.). The authors thank Dr.Richard Quinton (Newcastle, UK) and Dr. Francesca Fusco (Rome) for the support in critical reading of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

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Author notes

  1. Athina Samara

    Present address: University of Oslo and Norwegian Center for Stem Cell Research, 0317, Oslo, Norway

Authors and Affiliations

  1. Department of Pharmacological and Biomolecular Sciences, Section of Biomedicine and Endocrinology, and Centre of Excellence on Neurodegenerative Diseases (CEND), Università degli Studi di Milano, Via Balzaretti, 9, 20133, Milan, Italy

    Athina Samara, Mariarita Galbiati, Elio Messi & Roberto Maggi

  2. Endocrine Unit, Department of Clinical Physiopathology, Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies’ (DENOThe), University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy

    Paola Luciani, Cristiana Deledda & Alessandro Peri

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  1. Athina Samara
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Correspondence to Roberto Maggi.

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Samara, A., Galbiati, M., Luciani, P. et al. Altered expression of 3-betahydroxysterol delta-24-reductase/selective Alzheimer’s disease indicator-1 gene in Huntington’s disease models. J Endocrinol Invest 37, 729–737 (2014). https://doi.org/10.1007/s40618-014-0098-1

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  • DOI: https://doi.org/10.1007/s40618-014-0098-1

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