Mutant Alpha-Synuclein Causes Age-Dependent Neuropathology in Monkey Brain
文献类型：期刊论文
| 作者 | Yang WL1; Wang GH1,2; Wang CE2; Guo XY1; Yin P1; Gao JQ1; Tu ZC1; Wang ZB3; Wu J3; Hu XT3 |
| 刊名 | JOURNAL OF NEUROSCIENCE
 |
| 出版日期 | 2015 |
| 卷号 | 35期号:21页码:8345-8358 |
| 关键词 | aging degeneration neurite Parkinson's primate |
| 通讯作者 | xli2@emory.edu |
| 合作状况 | 其它 |
| 英文摘要 | Parkinson's disease (PD) is an age-dependent neurodegenerative disease that often occurs in those over age 60. Although rodents and small animals have been used widely to model PD and investigate its pathology, their short life span makes it difficult to assess the aging-related pathology that is likely to occur in PD patient brains. Here, we used brain tissues from rhesus monkeys at 2-3, 7-8, and >15 years of age to examine the expression of Parkin, PINK1, and alpha-synuclein, which are known to cause PD via loss-or gain-of-function mechanisms. We found that alpha-synuclein is increased in the older monkey brains, whereas Parkin and PINK1 are decreased or remain unchanged. Because of the gain of toxicity of alpha-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant alpha-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. A53T also causes more extensive reactive astrocytes and axonal degeneration in monkey brain than in mouse brain. Using monkey brain tissues, we found that A53T interacts with neurofascin, an adhesion molecule involved in axon subcellular targeting and neurite outgrowth. Aged monkey brain tissues show an increased interaction of neurofascin with A53T. Overexpression of A53T causes neuritic toxicity in cultured neuronal cells, which can be attenuated by transfected neurofascin. These findings from nonhuman primate brains reveal age-dependent pathological and molecular changes that could contribute to the age-dependent neuropathology in PD. |
| 收录类别 | SCI |
| 资助信息 | This work was supported by the National Key Basic Research Program of China (Grant 2012CBA01304), the National Natural Science Foundation of China (Grant 91332206), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant XDB13000000), the National Institutes of Health (Grants AG19206 and NS041449 to X.J.L.), and the State Key Laboratory of Molecular Developmental Biology, China. |
| 语种 | 英语 |
| 源URL | [http://159.226.149.26:8080/handle/152453/9219]  |
| 专题 | 昆明动物研究所_神经系统编码 |
| 作者单位 | 1.State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China, 2.Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, 3.Chinese Acad Sci, Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yang WL,Wang GH,Wang CE,et al. Mutant Alpha-Synuclein Causes Age-Dependent Neuropathology in Monkey Brain[J]. JOURNAL OF NEUROSCIENCE,2015,35(21):8345-8358. |
| APA | Yang WL.,Wang GH.,Wang CE.,Guo XY.,Yin P.,...&Li SH.(2015).Mutant Alpha-Synuclein Causes Age-Dependent Neuropathology in Monkey Brain.JOURNAL OF NEUROSCIENCE,35(21),8345-8358. |
| MLA | Yang WL,et al."Mutant Alpha-Synuclein Causes Age-Dependent Neuropathology in Monkey Brain".JOURNAL OF NEUROSCIENCE 35.21(2015):8345-8358. |
入库方式： OAI收割
来源：昆明动物研究所
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