Inhibitors of Leucine-Rich Repeat Kinase 2 (LRRK2): Progress and Promise for the Treatment of Parkinson's Disease

被引：16
|
作者：
Gilligan, Paul J. [1 ]
机构：
[1] Penn Drug Discovery Inst, Doylestown, PA 18902 USA
来源：
CURRENT TOPICS IN MEDICINAL CHEMISTRY | 2015年 / 15卷 / 10期
关键词：
Kinase inhibitors; Leucine-rich repeat kinase 2 (LRRK2); Parkinson's disease; ALPHA-SYNUCLEIN; GENE; MUTATIONS; G2019S; POTENT; DISCOVERY; PHOSPHORYLATION; EXPRESSION; FAMILIES; MODEL;
D O I：
10.2174/156802661510150328223655
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Mutations in the gene for leucine-rich repeat kinase 2 (LRRK2) have been linked to several familial and sporadic late-onset cases of Parkinson's disease. The cumulative data for the effects of mutant forms of this enzyme on neuronal degradation and the pathophysiology of Parkinson's disease create a compelling case for drug discovery based on inhibition of the mutant forms of LRRK2. This review focuses on structure-activity relationships for inhibitors of LRRK2 and the data supporting a potential role of these agents in treating Parkinson's disease.
引用
收藏
页码：927 / 938
页数：12
相关论文
共 50 条
  • [21] Dependence of Leucine-rich Repeat Kinase 2 (LRRK2) Kinase Activity on Dimerization
    Sen, Saurabh
    Webber, Philip J.
    West, Andrew B.
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (52) : 36346 - 36356
  • [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] Leucine-rich repeat kinase 2 (LRRK2) mutations in a Swedish Parkinson cohort and a healthy nonagenarian
    Belin, Andrea Carmine
    Westerlund, Marie
    Sydow, Olof
    Lundstromer, Karin
    Hakansson, Anna
    Nissbrandt, Hans
    Olson, Lars
    Galter, Dagmar
    MOVEMENT DISORDERS, 2006, 21 (10) : 1731 - 1734
  • [24] Leucine-rich repeat kinase 2 and Parkinson's disease
    Kang, Un-Beom
    Marto, Jarrod A.
    PROTEOMICS, 2017, 17 (1-2)
  • [25] A leucine-rich repeat kinase 2 (LRRK2) pathway biomarker characterization study in patients with Parkinson's disease with and without LRRK2 mutations and healthy controls
    Vissers, Maurits F. J. M.
    Troyer, Matthew D.
    Thijssen, Eva
    Heuberger, Jules A. A. C.
    Groeneveld, Geert Jan
    Huntwork-Rodriguez, Sarah
    CTS-CLINICAL AND TRANSLATIONAL SCIENCE, 2023, 16 (08): : 1408 - 1420
  • [26] The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation
    Greggio, Elisa
    Zambrano, Ibardo
    Kaganovich, Alice
    Beilina, Alexandra
    Taymans, Jean-Marc
    Daniels, Veronique
    Lewis, Patrick
    Jain, Shushant
    Ding, Jinhui
    Syed, Ali
    Thomas, Kelly J.
    Baekelandt, Veerle
    Cookson, Mark R.
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (24) : 16906 - 16914
  • [27] 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
  • [28] 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
  • [29] Screening and structural strategies for the design of selective Leucine-rich repeat kinase 2 (LRRK2) inhibitors
    Chen, Ijen
    David, Laurent
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2014, 248
  • [30] A meta-analysis of leucine-rich repeat kinase 2 (LRRK2) polymorphisms in Alzheimer's disease
    Fatahian, Reza
    Bagheri, Seyed Reza
    Sadeghi, Masoud
    FOLIA NEUROPATHOLOGICA, 2019, 57 (01) : 1 - 5
12345