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Altered Aconitase 2 Activity in Huntington’s Disease Peripheral Blood Cells and Mouse Model Striatum

Department of Neurology, Chang Gung Memorial Hospital, Linkou; Chang-Gung University College of Medicine, Taoyuan 33305, Taiwan
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(11), 2480; https://doi.org/10.3390/ijms18112480
Received: 26 October 2017 / Revised: 17 November 2017 / Accepted: 18 November 2017 / Published: 21 November 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Huntington’s disease (HD) is caused by an unstable cytosine adenine guanine (CAG) trinucleotide repeat expansion encoding a polyglutamine tract in the huntingtin protein. Previously, we identified several up- and down-regulated protein molecules in the striatum of the Hdh(CAG)150 knock-in mice at 16 months of age, a mouse model which is modeling the early human HD stage. Among those molecules, aconitase 2 (Aco2) located in the mitochondrial matrix is involved in the energy generation and susceptible to increased oxidative stress that would lead to inactivation of Aco2 activity. In this study, we demonstrate decreased Aco2 protein level and activity in the brain of both Hdh(CAG)150 and R6/2 mice. Aco2 activity was decreased in striatum of Hdh(CAG)150 mice at 16 months of age as well as R6/2 mice at 7 to 13 weeks of age. Aco2 activity in the striatum of R6/2 mice could be restored by the anti-oxidant, N-acetyl-l-cysteine, supporting that decreased Aco2 activity in HD is probably caused by increased oxidative damage. Decreased Aco2 activity was further found in the peripheral blood mononuclear cells (PBMC) of both HD patients and pre-symptomatic HD mutation (PreHD) carriers, while the decreased Aco2 protein level of PBMC was only present in HD patients. Aco2 activity correlated significantly with motor score, independence scale, and functional capacity of the Unified Huntington’s Disease Rating Scale as well as disease duration. Our study provides a potential biomarker to assess the disease status of HD patients and PreHD carriers. View Full-Text
Keywords: Huntington’s disease; Hdh(CAG)150 and R6/2 mice; peripheral blood mononuclear cells; aconitase 2; N-acetyl-l-cysteine; biomarker Huntington’s disease; Hdh(CAG)150 and R6/2 mice; peripheral blood mononuclear cells; aconitase 2; N-acetyl-l-cysteine; biomarker
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MDPI and ACS Style

Chen, C.-M.; Wu, Y.-R.; Chang, K.-H. Altered Aconitase 2 Activity in Huntington’s Disease Peripheral Blood Cells and Mouse Model Striatum. Int. J. Mol. Sci. 2017, 18, 2480. https://doi.org/10.3390/ijms18112480

AMA Style

Chen C-M, Wu Y-R, Chang K-H. Altered Aconitase 2 Activity in Huntington’s Disease Peripheral Blood Cells and Mouse Model Striatum. International Journal of Molecular Sciences. 2017; 18(11):2480. https://doi.org/10.3390/ijms18112480

Chicago/Turabian Style

Chen, Chiung-Mei, Yih-Ru Wu, and Kuo-Hsuan Chang. 2017. "Altered Aconitase 2 Activity in Huntington’s Disease Peripheral Blood Cells and Mouse Model Striatum" International Journal of Molecular Sciences 18, no. 11: 2480. https://doi.org/10.3390/ijms18112480

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