The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease

被引：424
|
作者：
Cookson, Mark R. [1 ]
机构：
[1] NIA, Neurogenet Lab, NIH, Bethesda, MD 20982 USA
来源：
NATURE REVIEWS NEUROSCIENCE | 2010年 / 11卷 / 12期
基金：
美国国家卫生研究院;
关键词：
AUTOSOMAL-DOMINANT PARKINSONISM; ALPHA-SYNUCLEIN; LEUCINE-RICH-REPEAT-KINASE-2; LRRK2; CYTOPLASMIC LOCALIZATION; 14-3-3; BINDING; ROC DOMAIN; MUTATIONS; PROTEIN; PHOSPHORYLATION; GENE;
D O I：
10.1038/nrn2935
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Parkinson's disease, like many common age-related conditions, is now recognized to have a substantial genetic component. Here, I discuss how mutations in a large complex gene-leucine-rich repeat kinase 2 (LRRK2) - affect protein function, and I review recent evidence that LRRK2 mutations affect pathways that involve other proteins that have been implicated in Parkinson's disease, specifically a-synuclein and tau. These concepts can be used to understand disease processes and to develop therapeutic opportunities for the treatment of Parkinson's disease.
引用
收藏
页码：791 / 797
页数：7
相关论文
共 50 条
  • [41] Hybrid enhanced sampling approaches to gain structural insights into leucine-rich repeat kinase 2 (LRRK2) Parkinson's disease mutation
    Ojha, Anupam A.
    Amaro, Rommie E.
    BIOPHYSICAL JOURNAL, 2023, 122 (03) : 187A - 187A
  • [42] Parkinson's (PD) disease linked leucine-rich repeat kinase 2 gene (LRRK2): A mixed lineage kinase with a potential role in vesicular trafficking and membrane recycling
    Dawson, Ted M. M.
    West, Anrew B.
    Moore, Darren J.
    Biskup, Saskia
    Smith, Wanli W.
    Celsi, Fulvio
    Bugayenko, Artem
    Pei, Zhong
    Jiang, Haibing
    Liang, Yideng
    Higashi, Shinji
    Andrabi, Shaida A.
    Kurkinen, Kaisa
    Yu, Seong Woon
    Savitt, Joseph M.
    Waldvogel, Henry J.
    Faull, Richard L. M.
    Emson, Piers C.
    Torp, Reidun
    Ottersen, Ole P.
    Ross, Christopher A.
    Dawson, Valina L.
    ANNALS OF NEUROLOGY, 2006, 60 : S52 - S52
  • [43] The tale of proteolysis targeting chimeras (PROTACs) for Leucine-Rich Repeat Kinase 2 (LRRK2)
    Konstantinidou, Markella
    Oun, Asmaa
    Pathak, Pragya
    Zhang, Bidong
    Wang, Zefeng
    ter Brake, Frans
    Dolga, Amalia M.
    Kortholt, Arjan
    Domling, Alexander
    CHEMMEDCHEM, 2021, 16 (06) : 959 - 965
  • [44] Potent, selective and orally bioavailable leucine-rich repeat kinase 2 (LRRK2) inhibitors
    Greshock, Thomas J.
    Sanders, John M.
    Drolet, Robert E.
    Rajapakse, Hemaka A.
    Chang, Ronald K.
    Kim, Boyoung
    Rada, Vanessa L.
    Tiscia, Heather E.
    Su, Hua
    Lai, Ming-Tain
    Sur, Sylvie M.
    Sanchez, Rosa I.
    Bilodeau, Mark T.
    Renger, John J.
    Kern, Jonathan T.
    McCauley, John A.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (11) : 2631 - 2635
  • [45] Identification and Characterization of a Leucine-Rich Repeat Kinase 2 (LRRK2) Consensus Phosphorylation Motif
    Pungaliya, Pooja P.
    Bai, Yuchen
    Lipinski, Kerri
    Anand, Vasanti S.
    Sen, Saurabh
    Brown, Eugene L.
    Bates, Brian
    Reinhart, Peter H.
    West, Andrew B.
    Hirst, Warren D.
    Braithwaite, Steven P.
    PLOS ONE, 2010, 5 (10):
  • [46] Missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene can cause late-onset Parkinson disease
    Daher, J. P. L.
    BRAIN PATHOLOGY, 2014, 24 : 71 - 72
  • [47] Patient-Control Association Study of the Leucine-Rich Repeat Kinase 2 (LRRK2) Gene in South African Parkinson's Disease Patients
    Bardien, Soraya
    Blanckenberg, Janine
    van der Merwe, Lize
    Farrer, Matthew J.
    Ross, Owen A.
    MOVEMENT DISORDERS, 2013, 28 (14) : 2039 - 2040
  • [48] Curcumin exposure induces expression of the Parkinson's disease-associated leucine-rich repeat kinase 2 (LRRK2) in rat mesencephalic cells
    Ortiz-Ortiz, Miguel A.
    Moran, Jose M.
    Ruiz-Mesa, Luz M.
    Niso-Santano, Mireia
    Bravo-SanPedro, Jose M.
    Gomez-Sanchez, Ruben
    Gonzalez-Polo, Rosa A.
    Fuentes, Jose M.
    NEUROSCIENCE LETTERS, 2010, 468 (02) : 120 - 124
  • [49] LEUCINE-RICH REPEAT KINASE2 (LRRK2) ASSOCIATED PARKINSON'S DISEASE: LESS VULNERABLE DURING COVID-19 PANDEMIC?
    Gharbi, A.
    Kacem, I.
    Sghaier, I.
    Mrabet, S.
    Souissi, A.
    Gargouri, A.
    Nasri, A.
    Gouider, R.
    PARKINSONISM & RELATED DISORDERS, 2023, 113 : 29 - 29
  • [50] Leucine-rich repeat kinase 2 and alternative splicing in Parkinson's disease
    Elliott, David A.
    Kim, Woojin S.
    Gorissen, Sarsha
    Halliday, Glenda M.
    Kwok, John B. J.
    MOVEMENT DISORDERS, 2012, 27 (08) : 1004 - 1011
12345