帕金森病是世界第二大老年神经退行性疾病，致病机理极为复杂。α-synuclein（α-syn）是帕金森病主要病理特征的路易小体的主要组成成分，其突变基因α-syn A30P 也与部分家族性帕金森相关。通过对过表达野生型人源α-syn WT 及其突变体α-syn A30P 蛋白的转基因小鼠的行为学检验、脑部纹状体中氧化应激水平以及儿茶酚胺异喹啉物质水平的检测，研究过表达α-syn 蛋白对小鼠纹状体产生的影响。结果显示转基因小鼠模型与正常鼠相比，其协调能力明显下降，纹状体与全脑的比例显著降低。同时，模型鼠脑中的氧化应激水平与儿茶酚胺异喹啉物质的表达水平均显著升高。研究结果说明，α-syn 蛋白及其突变体的过表达会引起小鼠脑部纹状体中氧化应激水平与儿茶酚异喹啉物质表达水平的升高，从而导致纹状体组织严重损伤。
Parkinson's disease (PD) is a common progressive neurodegenerative syndrome. The α- synuclein(α- syn)is a major protein constituent of Lewy bodies, and the α-syn A30P mutant causes familial autosomal dominant PD. In the present study, we explored the effect of α-syn overexpression and its mutant α-syn A30P on mice striatum. The behavior of PDGF-h α-synucleinWT and PDGF-h α-synucleinA30P transgenic mice was investigated, and the oxidative stress levels and the concentration of catecholamine isoquinolines (CAIQs) were determined in transgenic mice striatum, respectively. Compared to the control group, the coordination abilities of the two types of transgenic mice decreased. In addition, the level of oxidative stress and the concentration of CAIQs significantly increased in the overexpression of α-syn WT and α-syn A30P mice striatum. Thus, it is concluded that overexpression of α-syn and its mutant α-syn A30P exhibit impairment in the striatum through increasing the level of oxidative stress and CAIQs.
[1] Thomas B, Beal M F. Parkinson's disease[J]. Human Molecular Genetics, 2007, 16(R2): R183-R194.
[2] De Rijk M C, Launer L J, Berger K, et al. Prevalence of Parkinson's disease in Europe: A collaborative study of population-based cohorts. Neurologic diseases in the elderly research group[J]. Neurology, 2000, 54(11 S5): 21-23.
[3] Polymeropoulos M H, Higgins J J, Golbe L I, et al. Mapping of a gene for Parkinson's disease to chromosome 4q21-q23[J]. Science, 1996, 274 (5290): 1197-1199.
[4] Kruger R,KuhnW,MullerT,etal.Ala30Promutationinthegeneencoding α- synuclein in Parkinson's disease[J]. Nature Genetics, 1998, 18(2): 106-108.
[5] Zarranz J J, Alegre J, Gomez-Esteban J C, et al. The new mutation, E46K, of α-synuclein causes Parkinson and Lewy body dementia[J]. Annals of Neurology, 2004, 55(2): 164-173.
[6] Garcia-Reitbock P, Anichtchik O, Dalley J W, et al. Endogenous α- synuclein influences the number of dopaminergic neurons in mouse substantia nigra[J]. Experimental Neurology, 2013, 248: 541-545.
[7] George S, Rey N L, Reichenbach N, et al. α-Synuclein: the long distance runner[J]. Brain Pathology, 2013, 23(3): 350-357.
[8] Bendor J T, Logan T P, Edwards R H. The Function of α-Synuclein[J]. Neuron, 2013, 79(6): 1044-1066.
[9] Lotharius J, Brundin P. Pathogenesis of Parkinson's disease: Dopamine, vesicles and α-synuclein[J]. Nature Reviews Neuroscience, 2002, 3(12): 932-942.
[10] Lane E, Dunnett S. Animal models of Parkinson's disease and L-dopa induced dyskinesia: How close are we to the clinic?[J]. Psychopharma- cology, 2008, 199(3): 303-312.
[11] Blesa J, Phani S, Jackson-Lewis V, et al. Classic and new animal models of Parkinson's disease[J/OL]. Journal of Biomedicine & Bio- technology,2012,[2013-12-09]. http://dx.doi.org/10.1155/2012/845618.
[12] Krüger R, Kuhn W, Müller T, et al. AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's disease[J]. Nature Genetics, 1998, 18(2): 106-108.
[13] Chinta S J, Lieu C A, Demaria M, et al. Environmental stress, ageing and glial cell senescence: A novel mechanistic link to Parkinson's disease?[J]. Journal of Internal Medicine, 2013, 273(5): 429-436.
[14] Singleton A B, Farrer M J, Bonifati V. The genetics of Parkinson's disease: Progress and therapeutic implications[J]. Movement Disorders, 2013, 28(1): 14-23.
[15] Kang J H. Salsolinol, a catechol neurotoxin, induces oxidative modifi- cation of cytochrome c[J]. BMB Reports, 2013, 46(2): 119-123.
[16] Su Y, Duan J, Ying Z, et al. Increased vulnerability of parkin knock down PC12 cells to hydrogen peroxide toxicity: The role of salsolinol and NM-salsolinol[J]. Neuroscience, 2013, 233: 72-85.
[17] Witt S N, Flower T R. α-Synuclein, oxidative stress and apoptosis from the perspective of a yeast model of Parkinson's disease[J]. FEMS Yeast Research, 2006, 6(8): 1107-1116.
