Kingsbury Ann E, Daniel Susan E, Sangha Hardev, Eisen Sarah, Lees Andrew J, Foster Oliver J F
Queen Square Brain Bank for Neurological Disorders, Institute of Neurology, London, United Kingdom.
Mov Disord. 2004 Feb;19(2):162-70. doi: 10.1002/mds.10683.
The presynaptic protein alpha-synuclein is considered to play an important role in the pathophysiology of Parkinson's disease (PD). Point mutations in the alpha-synuclein gene have been demonstrated in familial PD and alpha-synuclein is a major component of Lewy bodies, the pathological hallmark of the sporadic disease. It is not clear whether abnormal accumulation of alpha-synuclein is the result of abnormal levels of expression of the gene in neurodegenerative conditions. Expression of alpha-synuclein mRNA was therefore studied in control and PD brain using semiquantitative in situ hybridization. alpha-synuclein was expressed widely and hybridization signal was seen in most cortical regions, hippocampus, cerebellum, and brain stem. There was little mRNA in the striatum and no hybridization signal was detected in glia. High levels of alpha-synuclein mRNA expression in neurons did not seem to be a marker for Lewy body formation. Abundant signal was seen both in regions in which Lewy body deposition occurs commonly in idiopathic PD (PD), such as substantia nigra and frontal and temporal cortex, as well as in less susceptible regions, e.g. visual cortex. Quantitative comparison of mRNA expression in regions of predilection for Lewy body formation showed that mRNA expression was reduced significantly in melanized substantia nigra neurons and frontal cortex neurons in Parkinson's disease. In substantia nigra neurons there seemed to be a negative correlation between cellular mRNA expression and disease duration. These findings are in broad agreement with other studies of the expression of alpha-synuclein mRNA in human brain and suggest that Lewy body formation is unlikely to be the result of overexpression of alpha-synuclein.
突触前蛋白α-突触核蛋白被认为在帕金森病（PD）的病理生理学中起重要作用。α-突触核蛋白基因的点突变已在家族性PD中得到证实，并且α-突触核蛋白是路易小体的主要成分，而路易小体是散发性疾病的病理标志。目前尚不清楚α-突触核蛋白的异常积聚是否是神经退行性疾病中该基因表达水平异常的结果。因此，使用半定量原位杂交技术研究了对照脑和PD脑中α-突触核蛋白mRNA的表达。α-突触核蛋白广泛表达，在大多数皮质区域、海马、小脑和脑干中均可见杂交信号。纹状体中mRNA很少，在胶质细胞中未检测到杂交信号。神经元中高水平的α-突触核蛋白mRNA表达似乎不是路易小体形成的标志物。在特发性PD（PD）中通常发生路易小体沉积的区域，如黑质、额叶和颞叶皮质，以及在较不易受影响的区域，如视觉皮质，均可见丰富的信号。对路易小体形成倾向区域的mRNA表达进行定量比较表明，帕金森病中黑质黑素化神经元和额叶皮质神经元中的mRNA表达显著降低。在黑质神经元中，细胞mRNA表达与疾病持续时间之间似乎存在负相关。这些发现与其他关于人脑中α-突触核蛋白mRNA表达的研究大致一致，并表明路易小体的形成不太可能是α-突触核蛋白过度表达的结果。
