Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease.
Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease.
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DOI：
10.1002/mds.26686
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发表时间：
2016-10
影响因子：
8.6
通讯作者：
West, Andrew B.
中科院分区：
文献类型：
--
作者：
Fraser, Kyle B.;Rawlins, Ashlee B.;Clark, Rachel G.;Alcalay, Roy N.;Standaert, David G.;Liu, Nianjun;West, Andrew B.
富含亮氨酸重复序列激酶2（LRRK 2）的突变增强了自磷酸化LRRK 2蛋白的水平，是遗传性帕金森病（PD）最常见的已知原因。在遗传关联研究中，LRRK 2进一步与特发性PD的易感性有关。比较生物库尿液样本中的自身磷酸化Ser（P）-1292 LRRK 2水平与PD和对照组的临床数据。从入选伯明翰亚拉巴马大学帕金森病生物标志物项目的79名PD和79名神经学健康对照的尿外泌体部分测量Ser（P）-1292 LRRK 2水平。Ser（P）-1292 LRRK 2水平在男性中高于女性（p<0.0001），并且与对照相比在PD中升高（p=0.0014）。Ser（P）-1292 LRRK 2水平在认知较差的PD患者中较高，并与莫卡中的表现较差相关（r=−0.2679 [−0.4628，−0.0482]），MDS-GRS分量表1和2（r=0.2239 [0.0014，0.4252]，0.3404 [0.1276，0.5233]），埃普沃思嗜睡量表（r=0.3215 [0.1066，0.5077]）和改良施瓦布和英格兰日常生活活动量表（r=-0.4455 [-0.6078，-0.2475]）。Ser（P）-1292 LRRK 2水平预测PD患者中认知功能障碍更严重的患者，具有一定的成功性（c=0.73）。尿外泌体Ser（P）-1292 LRRK 2水平在特发性PD中升高，并与认知障碍的严重程度和完成日常生活活动的困难相关。这些结果暗示了LRRK 2在特发性PD中的生化变化。
Mutations in Leucine-rich repeat kinase 2 (LRRK2) enhance levels of autophosphorylated LRRK2 protein and are the most common known cause of inherited Parkinson disease (PD). LRRK2 has been further implicated in susceptibility to idiopathic PD in genetic association studies. To compare autophosphorylated Ser(P)-1292 LRRK2 levels from biobanked urine samples with clinical data in PD and controls. Ser(P)-1292 LRRK2 levels were measured from urine exosome fractions from 79 PD and 79 neurologically healthy controls enrolled into the Parkinson Disease Biomarker Program at the University of Alabama at Birmingham. Ser(P)-1292 LRRK2 levels were higher in males than females (p<0.0001) and elevated in PD compared to controls (p=0.0014). Ser(P)-1292 LRRK2 levels were higher in PD cases with worse cognition and correlated with poor performance in MoCA (r=−0.2679 [−0.4628, −0.0482]), MDS-UPDRS subscales 1 and 2 (r=0.2239 [0.0014, 0,4252], 0.3404 [0.1276, 0.5233] respectively), Epworth Sleepiness Scale (r=0.3215 [0.1066, 0.5077]), and Modified Schwab and England Activities of Daily Living Scales (r=−0.4455 [−0.6078, −0.2475]). Ser(P)-1292 LRRK2 levels predicted those with worse cognitive impairment in PD patients with some success (c=0.73). Urinary exosome Ser(P)-1292 LRRK2 levels are elevated in idiopathic PD and correlated with the severity of cognitive impairment and difficultly in accomplishing activities of daily living. These results implicate biochemical changes in LRRK2 in idiopathic PD.
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影响因子：
8.6
作者：
Alcalay, Roy N.;Mirelman, Anat;Saunders-Pullman, Rachel;Tang, Ming-X;Mejia Santana, Helen;Raymond, Deborah;Roos, Ernest;Orbe-Reilly, Martha;Gurevich, Tanya;Bar Shira, Anat;Weisz, Mali Gana;Yasinovsky, Kira;Zalis, Maayan;Thaler, Avner;Deik, Andres;Barrett, Matthew James;Cabassa, Jose;Groves, Mark;Hunt, Ann L.;Lubarr, Naomi;San Luciano, Marta;Miravite, Joan;Palmese, Christina;Sachdev, Rivka;Sarva, Harini;Severt, Lawrence;Shanker, Vicki;Swan, Matthew Carrington;Soto-Valencia, Jeannie;Johannes, Brooke;Ortega, Robert;Fahn, Stanley;Cote, Lucien;Waters, Cheryl;Mazzoni, Pietro;Ford, Blair;Louis, Elan;Levy, Oren;Rosado, Llency;Ruiz, Diana;Dorovski, Tsvyatko;Pauciulo, Michael;Nichols, William;Orr-Urtreger, Avi;Ozelius, Laurie;Clark, Lorraine;Giladi, Nir;Bressman, Susan;Marder, Karen S.
通讯作者：
Marder, Karen S.
DOI：
10.1523/jneurosci.5601-11.2012
发表时间：
2012-02-01
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Moehle MS;Webber PJ;Tse T;Sukar N;Standaert DG;DeSilva TM;Cowell RM;West AB
通讯作者：
West AB
影响因子：
16.2
作者：
Chen-Plotkin, Alice S.
通讯作者：
Chen-Plotkin, Alice S.
影响因子：
5.6
作者：
Webber PJ;Smith AD;Sen S;Renfrow MB;Mobley JA;West AB
通讯作者：
West AB
影响因子：
7.3
作者：
Henderson, Jaclyn L.;Kormos, Bethany L.;Galatsis, Paul
通讯作者：
Galatsis, Paul