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Reduction of HIP2 expression causes motor function impairment and increased vulnerability to dopaminergic degeneration in Parkinson’s disease models
Huntingtin interaction protein 2 (HIP2) is an E2 ubiquitin-conjugating enzyme associated with neurodegenerative diseases, and HIP2 mRNA has been implicated as a potential blood biomarker for Parkinson’s disease (PD). However, it is unclear whether the alteration of HIP2 expression may contribute to...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170399/ https://www.ncbi.nlm.nih.gov/pubmed/30282965 http://dx.doi.org/10.1038/s41419-018-1066-z |
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author | Su, Jinlin Huang, Pei Qin, Meiling Lu, Qingqing Sang, Xiao Cai, Yijun Wang, Ying Liu, Fubing Wu, Rong Wang, Xiaoping Jiang, Xiaoxing Wang, Jian Sun, Qiang Chen, Shengdi Xu, Jin |
author_facet | Su, Jinlin Huang, Pei Qin, Meiling Lu, Qingqing Sang, Xiao Cai, Yijun Wang, Ying Liu, Fubing Wu, Rong Wang, Xiaoping Jiang, Xiaoxing Wang, Jian Sun, Qiang Chen, Shengdi Xu, Jin |
author_sort | Su, Jinlin |
collection | PubMed |
description | Huntingtin interaction protein 2 (HIP2) is an E2 ubiquitin-conjugating enzyme associated with neurodegenerative diseases, and HIP2 mRNA has been implicated as a potential blood biomarker for Parkinson’s disease (PD). However, it is unclear whether the alteration of HIP2 expression may contribute to the development of PD, and whether the change of HIP2 in blood could reflect its expression in the brain or motor functions in PD patients. In this study, we established a mouse line with HIP2 haploinsufficiency. The reduction of the HIP2 expression led to spontaneous motor function impairment and dopaminergic neuronal loss. Furthermore, HIP2 haploinsufficiency increased the susceptibility of mice to 6-hydroxydopamine (6-OHDA) and caused severe loss of dopaminergic neurons. Interestingly, in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model for PD, we observed concurrent, highly correlated decrease of HIP2 expression in the brain and in the blood. Using blood samples from more than 300 patients, we validated the decreased HIP2 mRNA in PD patients, including de novo patients. Finally, in a 1-year, 20-patient study, we observed reversed blood HIP2 mRNA levels accompanying improved motor and overall daily functions in 75% of the PD patients with instructed Tai Chi training. Therefore, our in vivo studies have indicated HIP2 insufficiency as a contributing factor for PD, and functionally validated blood HIP2 as a useful and reversible biomarker for PD. |
format | Online Article Text |
id | pubmed-6170399 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61703992018-10-09 Reduction of HIP2 expression causes motor function impairment and increased vulnerability to dopaminergic degeneration in Parkinson’s disease models Su, Jinlin Huang, Pei Qin, Meiling Lu, Qingqing Sang, Xiao Cai, Yijun Wang, Ying Liu, Fubing Wu, Rong Wang, Xiaoping Jiang, Xiaoxing Wang, Jian Sun, Qiang Chen, Shengdi Xu, Jin Cell Death Dis Article Huntingtin interaction protein 2 (HIP2) is an E2 ubiquitin-conjugating enzyme associated with neurodegenerative diseases, and HIP2 mRNA has been implicated as a potential blood biomarker for Parkinson’s disease (PD). However, it is unclear whether the alteration of HIP2 expression may contribute to the development of PD, and whether the change of HIP2 in blood could reflect its expression in the brain or motor functions in PD patients. In this study, we established a mouse line with HIP2 haploinsufficiency. The reduction of the HIP2 expression led to spontaneous motor function impairment and dopaminergic neuronal loss. Furthermore, HIP2 haploinsufficiency increased the susceptibility of mice to 6-hydroxydopamine (6-OHDA) and caused severe loss of dopaminergic neurons. Interestingly, in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model for PD, we observed concurrent, highly correlated decrease of HIP2 expression in the brain and in the blood. Using blood samples from more than 300 patients, we validated the decreased HIP2 mRNA in PD patients, including de novo patients. Finally, in a 1-year, 20-patient study, we observed reversed blood HIP2 mRNA levels accompanying improved motor and overall daily functions in 75% of the PD patients with instructed Tai Chi training. Therefore, our in vivo studies have indicated HIP2 insufficiency as a contributing factor for PD, and functionally validated blood HIP2 as a useful and reversible biomarker for PD. Nature Publishing Group UK 2018-10-03 /pmc/articles/PMC6170399/ /pubmed/30282965 http://dx.doi.org/10.1038/s41419-018-1066-z Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Su, Jinlin Huang, Pei Qin, Meiling Lu, Qingqing Sang, Xiao Cai, Yijun Wang, Ying Liu, Fubing Wu, Rong Wang, Xiaoping Jiang, Xiaoxing Wang, Jian Sun, Qiang Chen, Shengdi Xu, Jin Reduction of HIP2 expression causes motor function impairment and increased vulnerability to dopaminergic degeneration in Parkinson’s disease models |
title | Reduction of HIP2 expression causes motor function impairment and increased vulnerability to dopaminergic degeneration in Parkinson’s disease models |
title_full | Reduction of HIP2 expression causes motor function impairment and increased vulnerability to dopaminergic degeneration in Parkinson’s disease models |
title_fullStr | Reduction of HIP2 expression causes motor function impairment and increased vulnerability to dopaminergic degeneration in Parkinson’s disease models |
title_full_unstemmed | Reduction of HIP2 expression causes motor function impairment and increased vulnerability to dopaminergic degeneration in Parkinson’s disease models |
title_short | Reduction of HIP2 expression causes motor function impairment and increased vulnerability to dopaminergic degeneration in Parkinson’s disease models |
title_sort | reduction of hip2 expression causes motor function impairment and increased vulnerability to dopaminergic degeneration in parkinson’s disease models |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170399/ https://www.ncbi.nlm.nih.gov/pubmed/30282965 http://dx.doi.org/10.1038/s41419-018-1066-z |
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