Relationship among α-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra
Relationship among α-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra
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DOI：
10.1097/01.jnen.0000230520.47768.1a
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发表时间：
2006-08-01
影响因子：
3.2
通讯作者：
Wakabayashi, Koichi
中科院分区：
文献类型：
--
作者：
Mori, Fumiaki;Nishie, Makoto;Wakabayashi, Koichi
帕金森病（PD）的组织学标志是黑质（SN）和蓝斑（LC）中色素神经元的损失以及α-突触核蛋白（α S）的积累。据报道，酪氨酸羟化酶（TH）阴性的色素神经元存在于这些细胞核的PD患者。然而，TH免疫反应性和积累之间的关系仍然不确定。我们对PD患者（n = 10）和对照组（n = 7）的SN和LC进行了电化学检查。相关性研究表明，TH免疫反应性下降，US积累，神经元丢失之间的密切关系。此外，10%的色素neu 4。SN和LC中的54.9%含有异常US团聚体。此外，82.3%的着色神经元轴承的聚集体在SN和39.2%的那些在LC缺乏TH免疫反应，表明色素神经元在SN有一个更大的倾向，缺乏TH活性比那些在LC。最近的研究表明，TH活性的降低导致细胞毒性物质的减少，并且多巴胺合成的减少导致细胞毒性α S寡聚体的减少。因此，TH免疫反应性在色素神经元的减少，这里证明可以被认为是代表PD的细胞保护机制。
The histologic hallmark of Parkinson disease (PD) is loss of pigmented neurons in the substantia nigra (SN) and locus ceruleus (LC) with accumulation of a-synuclein (alpha S). It has been reported that tyrosine hydroxylase (TH)-negative pigmented neurons are present in these nuclei of patients with PD. However, the relationship between TH immunoreactivity and as accumulation remains uncertain. We immunohistochernically examined the SN and LC from patients with PD (n = 10) and control subjects (n = 7). A correlation study indicated a close relationship among decreased TH immunoreactivity, US accumulation, and neuronal loss. In addition, 10% of pigmented neu4. tons in the SN and 54.9% of those in the LC contained abnormal US aggregates. Moreover, 82.3% of pigmented neurons bearing as aggregates in the SN and 39.2% of those in the LC lacked TH immunoreactivity, suggesting that pigmented neurons in the SN have a greater tendency to lack TH activity than those in the LC. Recent studies have shown that this decrease of TH activity leads to a decrease of cytotoxic substances and that decreased dopamine synthesis leads to a reduction of cytotoxic alpha S oligomers. Therefore, the decrease of TH immunoreactivity in pigmented neurons demonstrated here can be considered to represent a cytoprotective mechanism in PD.