Motor impairment and aberrant production of neurochemicals in human α-synuclein A30P+A53T transgenic mice with α-synuclein pathology
Motor impairment and aberrant production of neurochemicals in human α-synuclein A30P+A53T transgenic mice with α-synuclein pathology
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DOI：
10.1016/j.brainres.2008.10.011
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发表时间：
2009-01-23
期刊：
影响因子：
2.9
通讯作者：
Shoji, Mikio
中科院分区：
文献类型：
--
作者：
Ikeda, Masaki;Kawarabayashi, Takeshi;Shoji, Mikio
在家族性帕金森病（PD）中已经发现了α-突触核蛋白（α SYN）基因的错义点突变、重复和三倍。家族性和散发性PD表现出α SYN病理的共同病理特征，例如，路易体（LB）和路易神经突（LN），以及黑质中多巴胺能神经元的丢失，导致运动障碍。为了阐明α SYN病理学的机制，我们产生了过表达人α SYN的Tg α SYN转基因小鼠，其在A30 P和A53 T中具有双重突变。人α-SYN在神经元、突起和异常神经元包涵体中广泛积累。肌氨酰不溶性α-SYN以及磷酸化、泛素化和硝化的α-SYN在大脑中积累。纹状体中多巴胺（DA）水平显著降低。在旋转棒试验中发现运动障碍。因此，Tg α SYN是一个有用的模型，用于分析从聚集的α SYN到运动障碍的病理级联反应，并可能用于药物试验。(C)2008年由Elsevier B. V.出版。
Missense point mutations, duplication and triplication in the alpha-synuclein (alpha SYN) gene have been identified in familial Parkinson's disease (PD). Familial and sporadic PD show common pathological features of alpha SYN pathologies, e.g., Lewy bodies (LBs) and Lewy neurites (LNs), and a loss of dopaminergic neurons in the substantia nigra that leads to motor disturbances. To elucidate the mechanism of alpha SYN pathologies, we generated Tg alpha SYN transgenic mice overexpressing human alpha SYN with double mutations in A30P and A53T. Human alpha SYN accumulated widely in neurons, processes and aberrant neuronal inclusion bodies. Sarcosyl-insoluble alpha SYN, as well as phosphorylated, ubiquitinated and nitrated alpha SYN, was accumulated in the brains. Significantly decreased levels of dopamine (DA) were recognized in the striatum. Motor impairment was revealed in a rotarod test. Thus, Tg alpha SYN is a useful model for analyzing the pathological cascade from aggregated alpha SYN to motor disturbance, and may be useful for drug trials. (C) 2008 Published by Elsevier B.V.