美国科学家最新研究发现，帕金森氏症的病因与控制多巴胺传导的“LRRK2”基因发生变异有关。
美国西奈山医学院的研究人员在新一期美国《神经科学杂志》（The Journal of Neuroscience ）上发表了上述研究成果。这一成果将有助于研究帕金森氏症的病理，寻找新的预防和治疗方法。
研究人员在研究经过基因改造的实验鼠时发现，“LRRK2”基因一旦发生变异，会使其丧失控制多巴胺传导的正常作用，结果导致实验鼠罹患帕金森氏症。
多巴胺是一种神经传递物质，主要负责大脑的情欲、感觉和兴奋等情绪的信息传递。
报告说，随着实验进一步深入，研究人员将研发治疗“LRRK2”基因变异的药物。
帕金森氏症是一种神经系统变性疾病，它会引起肌肉僵硬，以及手脚或身体其他部位的震颤。
推荐原文出处：
The Journal of Neuroscience doi:10.1523/JNEUROSCI.5604-09.2010
Enhanced Striatal Dopamine Transmission and Motor Performance with LRRK2 Overexpression in Mice Is Eliminated by Familial Parkinson's Disease Mutation G2019S
Xianting Li,1 Jyoti C. Patel,5 Jing Wang,1 Marat V. Avshalumov,4,5 Charles Nicholson,6 Joseph D. Buxbaum,2,3 Gregory A. Elder,3,7 Margaret E. Rice,5,6 and Zhenyu Yue1,2
Departments of 1Neurology, 2Neuroscience, 3Psychiatry, and 4Neurosurgery, Mount Sinai School of Medicine, New York, New York 10029, 5Departments of Neurosurgery and 6Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, and 7Rehabilitation Medicine Service, James J. Peters Department of Veterans Affairs Medical Center
PARK8/LRRK2 (leucine-rich repeat kinase 2) was recently identified as a causative gene for autosomal dominant Parkinson's disease (PD), with LRRK2 mutation G2019S linked to the most frequent familial form of PD. Emerging in vitro evidence indicates that aberrant enzymatic activity of LRRK2 protein carrying this mutation can cause neurotoxicity. However, the physiological and pathophysiological functions of LRRK2 in vivo remain elusive. Here we characterize two bacterial artificial chromosome (BAC) transgenic mouse strains overexpressing LRRK2 wild-type (Wt) or mutant G2019S. Transgenic LRRK2-Wt mice had elevated striatal dopamine (DA) release with unaltered DA uptake or tissue content. Consistent with this result, LRRK2-Wt mice were hyperactive and showed enhanced performance in motor function tests. These results suggest a role for LRRK2 in striatal DA transmission and the consequent motor function. In contrast, LRRK2-G2019S mice showed an age-dependent decrease in striatal DA content, as well as decreased striatal DA release and uptake. Despite increased brain kinase activity, LRRK2-G2019S overexpression was not associated with loss of DAergic neurons in substantia nigra or degeneration of nigrostriatal terminals at 12 months. Our results thus reveal a pivotal role for LRRK2 in regulating striatal DA transmission and consequent control of motor function. The PD-associated mutation G2019S may exert pathogenic effects by impairing these functions of LRRK2. Our LRRK2 BAC transgenic mice, therefore, could provide a useful model for understanding early PD pathological events.
