Altered Expression of 3-betahydroxysterol Delta-24-reductase/selective Alzheimer's Disease Indicator-1 Gene in Huntington's Disease Models

Overview

Journal J Endocrinol Invest

Publisher Springer

Specialty Endocrinology

Date 2014 Jun 12

PMID 24916565

Citations 5

Authors

Athina Samara

Mariarita Galbiati

Paola Luciani

Cristiana Deledda

Elio Messi

Alessandro Peri

Roberto Maggi

Affiliations

Soon will be listed here.

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.

Citing Articles

Cell-Type Specific Regulation of Cholesterogenesis by CYP46A1 Re-Expression in zQ175 HD Mouse Striatum.

Pinchaud K, Masson C, Dayre B, Mounier C, Gilles J, Vanhoutte P Int J Mol Sci. 2023; 24(13).

PMID: 37446179 PMC: 10341918. DOI: 10.3390/ijms241311001.

Altered Cholesterol Homeostasis in Huntington's Disease.

Kacher R, Mounier C, Caboche J, Betuing S Front Aging Neurosci. 2022; 14:797220.

PMID: 35517051 PMC: 9063567. DOI: 10.3389/fnagi.2022.797220.

The role of DHCR24 in the pathogenesis of AD: re-cognition of the relationship between cholesterol and AD pathogenesis.

Bai X, Mai M, Yao K, Zhang M, Huang Y, Zhang W Acta Neuropathol Commun. 2022; 10(1):35.

PMID: 35296367 PMC: 8925223. DOI: 10.1186/s40478-022-01338-3.

Oxidative Stress and Neurodegeneration: Interconnected Processes in PolyQ Diseases.

Gkekas I, Gioran A, Boziki M, Grigoriadis N, Chondrogianni N, Petrakis S Antioxidants (Basel). 2021; 10(9).

PMID: 34573082 PMC: 8471619. DOI: 10.3390/antiox10091450.

Striatal infusion of cholesterol promotes dose-dependent behavioral benefits and exerts disease-modifying effects in Huntington's disease mice.

Birolini G, Valenza M, Di Paolo E, Vezzoli E, Talpo F, Maniezzi C EMBO Mol Med. 2020; 12(10):e12519.

PMID: 32959531 PMC: 7539329. DOI: 10.15252/emmm.202012519.

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