Neurotoxicity and behavioral deficits associated with Septin 5 accumulation in dopaminergic neurons
Neurotoxicity and behavioral deficits associated with Septin 5 accumulation in dopaminergic neurons
复制标题
DOI：
10.1111/j.1471-4159.2005.03257.x
复制
发表时间：
2005-08-01
影响因子：
4.7
通讯作者：
Peng, C
中科院分区：
文献类型：
--
作者：
Son, JH;Kawamata, H;Peng, C
parkin底物Septin 5是一种囊泡和膜相关蛋白，在抑制胞吐中起重要作用。Septin 5对黑质（SN）多巴胺能（DAergic）神经元的调节作用维持在相对较低的水平，目前尚未明确。由于帕金森氏症的功能丧失突变是家族性帕金森氏病的主要原因，一种普遍的假设是，帕金森氏症活性的丧失导致Septin 5的积累，从而赋予sn -能神经元神经元特异性毒性。体外和体内模型被用来支持这一假设。在我们的DAergic SN4741细胞模型中，Septin 5而非synphilin-1（另一种parkin底物）水平升高的急性积累导致细胞毒性细胞死亡，而parkin共转染显著降低了细胞毒性细胞死亡。转基因
Septin 5, a parkin substrate, is a vesicle- and membrane-associated protein that plays a significant role in inhibiting exocytosis. The regulatory function of Septin 5 in dopaminergic (DAergic) neurons of substantia nigra (SN), maintained at relatively low levels, has not yet been delineated. As loss of function mutations of parkin are the principal cause of a familial Parkinson's disease, a prevailing hypothesis is that the loss of parkin activity results in accumulation of Septin 5 which confers neuron-specific toxicity in SN-DAergic neurons. In vitro and in vivo models were used to support this hypothesis. In our well-characterized DAergic SN4741 cell model, acute accumulation of elevated levels of Septin 5, but not synphilin-1 ( another parkin substrate), resulted in cytotoxic cell death that was markedly reduced by parkin co-transfection. A transgenic