美國科學家最新研究發(fā)現(xiàn),，帕金森氏癥的病因與控制多巴胺傳導的“LRRK2”基因發(fā)生變異有關,。
美國西奈山醫(yī)學院的研究人員在新一期美國《神經(jīng)科學雜志》（The Journal of Neuroscience ）上發(fā)表了上述研究成果,。這一成果將有助于研究帕金森氏癥的病理,，尋找新的預防和治療方法,。
研究人員在研究經(jīng)過基因改造的實驗鼠時發(fā)現(xiàn),，“LRRK2”基因一旦發(fā)生變異,，會使其喪失控制多巴胺傳導的正常作用,，結果導致實驗鼠罹患帕金森氏癥。
多巴胺是一種神經(jīng)傳遞物質,，主要負責大腦的情欲,、感覺和興奮等情緒的信息傳遞。
報告說,，隨著實驗進一步深入,，研究人員將研發(fā)治療“LRRK2”基因變異的藥物。
帕金森氏癥是一種神經(jīng)系統(tǒng)變性疾病,，它會引起肌肉僵硬,，以及手腳或身體其他部位的震顫。(生物谷Bioon.com)
生物谷推薦原文出處：
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.
