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
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
  • [21] Evaluation of Current Methods to Detect Cellular Leucine-Rich Repeat Kinase 2 (LRRK2) Kinase Activity
    Fernandez, Belen
    Chittoor-Vinod, Vinita G.
    Kluss, Jillian H.
    Kelly, Kaela
    Bryant, Nicole
    Nguyen, An Phu Tran
    Bukhari, Syed A.
    Smith, Nathan
    Ordonez, Antonio Jesus Lara
    Fdez, Elena
    Chartier-Harlin, Marie-Christine
    Montine, Thomas J.
    Wilson, Mark A.
    Moore, Darren J.
    West, Andrew B.
    Cookson, Mark R.
    Nichols, R. Jeremy
    Hilfiker, Sabine
    JOURNAL OF PARKINSONS DISEASE, 2022, 12 (05) : 1423 - 1447
  • [22] Effect of leucine-rich repeat kinase 2 (LRRK2) on protein synthesis
    Kim, Hyejung
    Son, Ilhong
    Seol, Wongi
    ANIMAL CELLS AND SYSTEMS, 2018, 22 (01) : 15 - 21
  • [23] Identification of chemicals to inhibit the kinase activity of leucine-rich repeat kinase 2 (LRRK2), a Parkinson's disease-associated protein
    Yun, HyeJin
    Heo, Hye Young
    Kim, Hyun Ha
    DooKim, Nam
    Seol, Wongi
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (10) : 2953 - 2957
  • [24] The Parkinson's disease-associated protein, leucine-rich repeat kinase 2 (LRRK2), is an authentic GTPase that stimulates kinase activity
    Guo, Luxuan
    Gandhi, Payal N.
    Wang, Wen
    Petersen, Robert B.
    Wilson-Delfosse, Amy L.
    Chen, Shu G.
    EXPERIMENTAL CELL RESEARCH, 2007, 313 (16) : 3658 - 3670
  • [25] The development of inhibitors of leucine-rich repeat kinase 2 (LRRK2) as a therapeutic strategy for Parkinson's disease: the current state of play
    Azeggagh, Sonia
    Berwick, Daniel C.
    BRITISH JOURNAL OF PHARMACOLOGY, 2022, 179 (08) : 1478 - 1495
  • [26] 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):
  • [27] Hypothesis: Do miRNAs Targeting the Leucine-Rich Repeat Kinase 2 Gene (LRRK2) Influence Parkinson's Disease Susceptibility?
    Yilmaz, Senay Gorucu
    Geyik, Sirma
    Neyal, Ayse Munife
    Soko, Nyarai D.
    Bozkurt, Hakan
    Dandara, Collet
    OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY, 2016, 20 (04) : 224 - 228
  • [28] 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
  • [29] 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
  • [30] Analysis of Leucine-rich repeat kinase 2 (LRRK2) and Parkinson protein 2 (parkin, PARK2) genes mutations in Slovak Parkinson disease patients
    Bognar, Csaba
    Baldovic, Marian
    Benetin, Jan
    Kadasi, Ludovit
    Zatkova, Andrea
    GENERAL PHYSIOLOGY AND BIOPHYSICS, 2013, 32 (01) : 55 - 66