Fornai Francesco, Lenzi Paola, Ferrucci Michela, Lazzeri Gloria, di Poggio Adolfo Bandettini, Natale Gianfranco, Busceti Carla L, Biagioni Francesca, Giusiani Mario, Ruggieri Stefano, Paparelli Antonio
Department of Human Morphology and Applied Biology, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
Brain Res Bull. 2005 May 15;65(5):405-13. doi: 10.1016/j.brainresbull.2005.02.022.
In recent years several clinical and research findings have demonstrated the involvement of the presynaptic protein alpha-synuclein in a variety of neurodegenerative disorders which are known as synucleinopathies. Although the function of this protein in the physiology of the cell remains unknown, it is evident that both genetic alterations or a mere overexpression of the native molecule produces a degeneration of nigral dopamine-containing neurons leading to movement disorders, as demonstrated in inherited Parkinson's disease. In the present study, we investigated whether widely abused drugs such as methamphetamine and methylenedioxymethamphetamine (ecstasy), which are known to damage the nigrostriatal dopamine pathway of mice, increase the expression of alpha-synuclein within dopamine neurons of the substantia nigra pars compacta. The results of this study demonstrate that nigrostriatal dopamine denervation and occurrence of intracellular inclusions in nigral neurons produced by amphetamine derivatives are related to increased expression of alpha-synuclein within dopamine neurons of the substantia nigra. This lends substance to the hypothesis that increased amounts of native alpha-synuclein may be per se a detrimental factor for the dopamine neurons.
近年来，多项临床和研究结果表明，突触前蛋白α-突触核蛋白参与了多种神经退行性疾病，即突触核蛋白病。尽管该蛋白在细胞生理学中的功能尚不清楚，但很明显，基因改变或天然分子的单纯过度表达都会导致含黑质多巴胺能神经元变性，进而引发运动障碍，遗传性帕金森病就是例证。在本研究中，我们调查了广泛滥用的药物，如甲基苯丙胺和亚甲二氧基甲基苯丙胺（摇头丸），已知这些药物会损害小鼠的黑质纹状体多巴胺通路，是否会增加黑质致密部多巴胺能神经元内α-突触核蛋白的表达。本研究结果表明，苯丙胺衍生物导致的黑质纹状体多巴胺去神经支配和黑质神经元内细胞内包涵体的出现，与黑质多巴胺能神经元内α-突触核蛋白表达增加有关。这支持了这样一种假说，即天然α-突触核蛋白数量增加本身可能是多巴胺能神经元的一个有害因素。
