Murphy D D, Rueter S M, Trojanowski J Q, Lee V M
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA.
J Neurosci. 2000 May 1;20(9):3214-20. doi: 10.1523/JNEUROSCI.20-09-03214.2000.
alpha-, beta-, and gamma-Synuclein, a novel family of neuronal proteins, has become the focus of research interest because alpha-synuclein has been increasingly implicated in the pathogenesis of Parkinson's and Alzheimer's disease. However, the normal functions of the synucleins are still unknown. For this reason, we characterized alpha-, beta-, and gamma-synuclein expression in primary hippocampal neuronal cultures and showed that the onset of alpha- and beta-synuclein expression was delayed after synaptic development, suggesting that these synucleins may not be essential for synapse formation. In mature cultured primary neurons, alpha- and beta-synuclein colocalized almost exclusively with synaptophysin in the presynaptic terminal, whereas little gamma-synuclein was expressed at all. To assess the function of alpha-synuclein, we suppressed expression of this protein with antisense oligonucleotide technology. Morphometric ultrastructural analysis of the alpha-synuclein antisense oligonucleotide-treated cultures revealed a significant reduction in the distal pool of synaptic vesicles. These data suggest that one function of alpha-synuclein may be to regulate the size of distinct pools of synaptic vesicles in mature neurons.
α-、β-和γ-突触核蛋白是一类新的神经元蛋白家族，已成为研究热点，因为α-突触核蛋白越来越多地被认为与帕金森病和阿尔茨海默病的发病机制有关。然而，突触核蛋白的正常功能仍不清楚。因此，我们对原代海马神经元培养物中α-、β-和γ-突触核蛋白的表达进行了表征，结果显示α-和β-突触核蛋白的表达在突触发育后延迟开始，这表明这些突触核蛋白可能对突触形成并非必不可少。在成熟的原代培养神经元中，α-和β-突触核蛋白几乎仅与突触前末端的突触素共定位，而几乎不表达γ-突触核蛋白。为了评估α-突触核蛋白的功能，我们使用反义寡核苷酸技术抑制该蛋白的表达。对经α-突触核蛋白反义寡核苷酸处理的培养物进行形态计量超微结构分析发现，突触小泡的远端池显著减少。这些数据表明，α-突触核蛋白的一个功能可能是调节成熟神经元中不同突触小泡池的大小。
