Elevated Hapln2 expression contributes to protein aggregation and neurodegeneration in an animal model of Parkinson's disease
Parkinson’s disease (PD), the second most common age-associated progressive neurodegenerative disorder, is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SN). The pathogenesis of PD and the mechanisms underlying the degeneration of DA neurons are still...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-08-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnagi.2016.00197/full |
| _version_ | 1811235432783937536 |
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| author | Qinqin Wang Qinqin Wang Qinbo Zhou Shuzhen Zhang Wei Shao Yanqing Yin Yandong Li Jincan Hou Xinhua Zhang Yongshun Guo Xiaomin Wang Xiaosong Gu Jiawei Zhou |
| author_facet | Qinqin Wang Qinqin Wang Qinbo Zhou Shuzhen Zhang Wei Shao Yanqing Yin Yandong Li Jincan Hou Xinhua Zhang Yongshun Guo Xiaomin Wang Xiaosong Gu Jiawei Zhou |
| author_sort | Qinqin Wang |
| collection | DOAJ |
| description | Parkinson’s disease (PD), the second most common age-associated progressive neurodegenerative disorder, is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SN). The pathogenesis of PD and the mechanisms underlying the degeneration of DA neurons are still not fully understood. Our previous quantitative proteomics study revealed that hyaluronan and proteoglycan binding link protein 2 (Hapln2) is one of differentially expressed proteins in the substantia nigra tissues from PD patients and healthy control subjects. However, the potential role of Hapln2 in PD pathogenesis remains elusive. In the present study, we characterized the expression pattern of Hapln2. In situ hybridization revealed that Hapln2 mRNA was widely expressed in adult rat brain with high abundance in the substantia nigra. Immunoblotting showed that expression levels of Hapln2 were markedly upregulated in the substantia nigra of either human subjects with Parkinson’s disease compared with healthy control. Likewise, there were profound increases in Hapln2 expression in neurotoxin 6-hydroxydopamine-treated rat. Overexpression of Hapln2 in vitro increased vulnerability of MES23.5 cells, a dopaminergic cell line, to 6-hydroxydopamine. Moreover, Hapln2 overexpression led to the formation of cytoplasmic aggregates which were co-localized with ubiquitin and E3 ligases including Parkin, Gp78 and Hrd1 in vitro. Endogenous α-synuclein was also localized in Hapln2-containing aggregates and ablation of Hapln2 led to a marked decrease in levels of α-synuclein in insoluble fraction compared with control. Thus, Hapln2 is identified as a novel factor contributing to neurodegeneration in PD. Our data provides new insights into the cellular mechanism underlying the pathogenesis in PD. |
| first_indexed | 2024-04-12T11:50:49Z |
| format | Article |
| id | doaj.art-cadf3683b0ee43c990e8a45f41d6361a |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-12T11:50:49Z |
| publishDate | 2016-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-cadf3683b0ee43c990e8a45f41d6361a2022-12-22T03:34:10ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652016-08-01810.3389/fnagi.2016.00197212080Elevated Hapln2 expression contributes to protein aggregation and neurodegeneration in an animal model of Parkinson's diseaseQinqin Wang0Qinqin Wang1Qinbo Zhou2Shuzhen Zhang3Wei Shao4Yanqing Yin5Yandong Li6Jincan Hou7Xinhua Zhang8Yongshun Guo9Xiaomin Wang10Xiaosong Gu11Jiawei Zhou12Shanghai Institutes for Biological Sciences Chinese Academy of SciencesGraduate School of University of Chinese Academy of ScienceShanghai Institutes for Biological Sciences Chinese Academy of SciencesShanghai Institutes for Biological Sciences Chinese Academy of SciencesShanghai Institutes for Biological Sciences Chinese Academy of SciencesShanghai Institutes for Biological Sciences Chinese Academy of SciencesShanghai Institutes for Biological Sciences Chinese Academy of SciencesShanghai Institutes for Biological Sciences Chinese Academy of SciencesSchool of Medicine, Nantong UniversityBeijing Institute for Brain DisordersBeijing Institute for Brain DisordersSchool of Medicine, Nantong UniversityShanghai Institutes for Biological Sciences Chinese Academy of SciencesParkinson’s disease (PD), the second most common age-associated progressive neurodegenerative disorder, is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SN). The pathogenesis of PD and the mechanisms underlying the degeneration of DA neurons are still not fully understood. Our previous quantitative proteomics study revealed that hyaluronan and proteoglycan binding link protein 2 (Hapln2) is one of differentially expressed proteins in the substantia nigra tissues from PD patients and healthy control subjects. However, the potential role of Hapln2 in PD pathogenesis remains elusive. In the present study, we characterized the expression pattern of Hapln2. In situ hybridization revealed that Hapln2 mRNA was widely expressed in adult rat brain with high abundance in the substantia nigra. Immunoblotting showed that expression levels of Hapln2 were markedly upregulated in the substantia nigra of either human subjects with Parkinson’s disease compared with healthy control. Likewise, there were profound increases in Hapln2 expression in neurotoxin 6-hydroxydopamine-treated rat. Overexpression of Hapln2 in vitro increased vulnerability of MES23.5 cells, a dopaminergic cell line, to 6-hydroxydopamine. Moreover, Hapln2 overexpression led to the formation of cytoplasmic aggregates which were co-localized with ubiquitin and E3 ligases including Parkin, Gp78 and Hrd1 in vitro. Endogenous α-synuclein was also localized in Hapln2-containing aggregates and ablation of Hapln2 led to a marked decrease in levels of α-synuclein in insoluble fraction compared with control. Thus, Hapln2 is identified as a novel factor contributing to neurodegeneration in PD. Our data provides new insights into the cellular mechanism underlying the pathogenesis in PD.http://journal.frontiersin.org/Journal/10.3389/fnagi.2016.00197/fullDopaminergic NeuronsParkinson’s diseaseubiquitin-proteasome systemAggregation.hyaluronan and proteoglycan binding link protein 2 |
| spellingShingle | Qinqin Wang Qinqin Wang Qinbo Zhou Shuzhen Zhang Wei Shao Yanqing Yin Yandong Li Jincan Hou Xinhua Zhang Yongshun Guo Xiaomin Wang Xiaosong Gu Jiawei Zhou Elevated Hapln2 expression contributes to protein aggregation and neurodegeneration in an animal model of Parkinson's disease Frontiers in Aging Neuroscience Dopaminergic Neurons Parkinson’s disease ubiquitin-proteasome system Aggregation. hyaluronan and proteoglycan binding link protein 2 |
| title | Elevated Hapln2 expression contributes to protein aggregation and neurodegeneration in an animal model of Parkinson's disease |
| title_full | Elevated Hapln2 expression contributes to protein aggregation and neurodegeneration in an animal model of Parkinson's disease |
| title_fullStr | Elevated Hapln2 expression contributes to protein aggregation and neurodegeneration in an animal model of Parkinson's disease |
| title_full_unstemmed | Elevated Hapln2 expression contributes to protein aggregation and neurodegeneration in an animal model of Parkinson's disease |
| title_short | Elevated Hapln2 expression contributes to protein aggregation and neurodegeneration in an animal model of Parkinson's disease |
| title_sort | elevated hapln2 expression contributes to protein aggregation and neurodegeneration in an animal model of parkinson 39 s disease |
| topic | Dopaminergic Neurons Parkinson’s disease ubiquitin-proteasome system Aggregation. hyaluronan and proteoglycan binding link protein 2 |
| url | http://journal.frontiersin.org/Journal/10.3389/fnagi.2016.00197/full |
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