Athina Samara1,2, Mariarita Galbiati1, Paola Luciani3, Cristiana Deledda3, Elio Messi1, Alessandro Peri3, Roberto Maggi4. 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. 2. University of Oslo and Norwegian Center for Stem Cell Research, 0317, Oslo, Norway. 3. 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. 4. 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. roberto.maggi@unimi.it.
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.
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 HDmouse 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 HDpatients. CONCLUSIONS: In conclusion, these results support the hypothesis of a possible role of DHCR24 in HD.
Authors: D Sarkar; T Imai; F Kambe; A Shibata; S Ohmori; A Siddiq; S Hayasaka; H Funahashi; H Seo Journal: J Clin Endocrinol Metab Date: 2001-11 Impact factor: 5.958
Authors: Katrin Kuehnle; Arames Crameri; Roland E Kälin; Paola Luciani; Susanna Benvenuti; Alessandro Peri; Francesca Ratti; Monica Rodolfo; Luka Kulic; Frank L Heppner; Roger M Nitsch; M Hasan Mohajeri Journal: Mol Cell Biol Date: 2007-11-05 Impact factor: 4.272