Hurley M J, Patel P H, Jackson M J, Smith L A, Rose S, Jenner P
Neurodegenerative Diseases Research Group, Pharmaceutical Sciences Research Division, School of Biomedical and Health Sciences, King's College, London SE1 1UL, UK.
Eur J Neurosci. 2007 Jul;26(1):171-7. doi: 10.1111/j.1460-9568.2007.05638.x.
The level of leucine-rich repeat kinase 2 (Lrrk2) mRNA expression was measured by reverse transcription-polymerase chain reaction in anterior striatum from normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets (Callithrix jacchus) that had L-3,4-dihydroxyphenylalanine methyl ester (L-DOPA)-induced dyskinesia. The level of striatal Lrrk2 mRNA was increased in MPTP-treated common marmosets that had L-DOPA-induced dyskinesia compared with normal animals that did not receive l-DOPA. Marmosets that exhibited higher levels of dyskinesia had the greatest increase in striatal Lrrk2 mRNA. Lrrk2 mRNA expression was also measured in human striatum and substantia nigra from control subjects and patients dying with Parkinson's disease. In contrast to marmoset tissue, no alteration in Lrrk2 mRNA expression was found in parkinsonian human brain. However, the brain was from patients who had an overall low level of dyskinesia. The correlation between striatal Lrrk2 mRNA levels in MPTP-treated common marmoset striatum and L-DOPA-induced dyskinesia indicates that LRRK2 may have a role in the molecular alterations that cause L-DOPA-induced dyskinesia.
采用逆转录-聚合酶链反应检测正常普通狨猴(绢毛猴)以及经1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)处理且出现左旋多巴甲酯(L-DOPA)诱导性运动障碍的普通狨猴纹状体前部中富含亮氨酸重复序列激酶2(Lrrk2)的mRNA表达水平。与未接受L-DOPA的正常动物相比,经MPTP处理且出现L-DOPA诱导性运动障碍的普通狨猴纹状体Lrrk2 mRNA水平升高。运动障碍水平较高的狨猴纹状体Lrrk2 mRNA增加幅度最大。还检测了对照组受试者以及死于帕金森病患者的人类纹状体和黑质中Lrrk2 mRNA的表达。与狨猴组织不同,帕金森病患者大脑中未发现Lrrk2 mRNA表达有改变。然而,这些大脑来自运动障碍总体水平较低的患者。MPTP处理的普通狨猴纹状体中Lrrk2 mRNA水平与L-DOPA诱导性运动障碍之间的相关性表明,LRRK2可能在导致L-DOPA诱导性运动障碍的分子改变中起作用。