少突胶质细胞中α-突触核蛋白表达导致神经胶质和神经元变性的多系统萎缩小鼠模型。
Mouse model of multiple system atrophy alpha-synuclein expression in oligodendrocytes causes glial and neuronal degeneration.
作者信息
Yazawa Ikuru, Giasson Benoit I, Sasaki Ryogen, Zhang Bin, Joyce Sonali, Uryu Kunihiro, Trojanowski John Q, Lee Virginia M-Y
机构信息
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
出版信息
Neuron. 2005 Mar 24;45(6):847-59. doi: 10.1016/j.neuron.2005.01.032.
Transgenic (Tg) mice overexpressing human wild-type alpha-synuclein in oligodendrocytes under the control of the 2,' 3'-cyclic nucleotide 3'-phosphodiesterase (CNP) promoter are shown here to recapitulate features of multiple system atrophy (MSA), including the accumulation of filamentous human alpha-synuclein aggregates in oligodendrocytes linked to their degeneration and autophagocytosis of myelin. Significantly, endogenous mouse alpha-synuclein also accumulated in normal and degenerating axons and axon terminals in association with oligodendroglia and neuron loss and slowly progressive motor impairments. Our studies demonstrate that overexpression of alpha-synuclein in oligodendrocytes of mice results in MSA-like degeneration in the CNS and that alpha-synuclein inclusions in oligodendrocytes participate in the degeneration of neurons in MSA.
在此展示，在2'，3'-环核苷酸3'-磷酸二酯酶（CNP）启动子控制下，少突胶质细胞中过表达人野生型α-突触核蛋白的转基因（Tg）小鼠重现了多系统萎缩（MSA）的特征，包括丝状人α-突触核蛋白聚集体在少突胶质细胞中的积累，这与它们的变性以及髓鞘的自噬作用有关。值得注意的是，内源性小鼠α-突触核蛋白也在正常和变性的轴突及轴突终末中积累，伴有少突胶质细胞和神经元丢失以及缓慢进展的运动障碍。我们的研究表明，小鼠少突胶质细胞中α-突触核蛋白的过表达导致中枢神经系统出现类似MSA的变性，并且少突胶质细胞中的α-突触核蛋白包涵体参与了MSA中神经元的变性。
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