Inhibition of LRRK2 kinase activity stimulates macroautophagy.

PubWeight™: 0.98‹?› | Rank: Top 15%

🔗 View Article (PMC 3898616)

Published in Biochim Biophys Acta on August 01, 2013

Authors

Claudia Manzoni1, Adamantios Mamais2, Sybille Dihanich3, Rosella Abeti3, Marc P M Soutar3, Helene Plun-Favreau3, Paola Giunti3, Sharon A Tooze4, Rina Bandopadhyay2, Patrick A Lewis5

Author Affiliations

1: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK. Electronic address: c.manzoni@ucl.ac.uk.
2: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK; Reta Lila Weston Institute and Queen Square Brain Bank, UCL Institute of Neurology, 1 Wakefield Street, London, WC1N 1PJ, UK.
3: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
4: London Research Institute, Cancer Research UK, Lincoln's Inn Fields, London, WC2A 3LY, UK.
5: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK; School of Pharmacy, University of Reading, Whiteknights, Reading, RG6 6AP, UK. Electronic address: patrick.lewis@ucl.ac.uk.

Articles citing this

Autophagy and neurodegeneration. J Clin Invest (2015) 1.24

LRRK2 and neuroinflammation: partners in crime in Parkinson's disease? J Neuroinflammation (2014) 1.05

Membrane recruitment of endogenous LRRK2 precedes its potent regulation of autophagy. Hum Mol Genet (2014) 0.98

Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice. Neurobiol Dis (2015) 0.97

Cross-cancer profiling of molecular alterations within the human autophagy interaction network. Autophagy (2015) 0.94

Autophagy in neurodegenerative diseases: from mechanism to therapeutic approach. Mol Cells (2015) 0.92

Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance. J Neurochem (2016) 0.91

LRRK2, a puzzling protein: insights into Parkinson's disease pathogenesis. Exp Neurol (2014) 0.88

Pathogenic Parkinson's disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation. Biochem Biophys Res Commun (2013) 0.87

Cellular processes associated with LRRK2 function and dysfunction. FEBS J (2015) 0.86

Computational analysis of the LRRK2 interactome. PeerJ (2015) 0.86

The LRRK2 inhibitor GSK2578215A induces protective autophagy in SH-SY5Y cells: involvement of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS signaling. Cell Death Dis (2014) 0.86

The role of the LRRK2 gene in Parkinsonism. Mol Neurodegener (2014) 0.85

The G2019S LRRK2 mutation increases myeloid cell chemotactic responses and enhances LRRK2 binding to actin-regulatory proteins. Hum Mol Genet (2015) 0.83

Association of the LRRK2 genetic polymorphisms with leprosy in Han Chinese from Southwest China. Genes Immun (2014) 0.82

Impaired mitochondrial homeostasis and neurodegeneration: towards new therapeutic targets? J Bioenerg Biomembr (2014) 0.80

Deconvoluting the complexity of autophagy and Parkinson's disease for potential therapeutic purpose. Oncotarget (2015) 0.78

mTOR independent regulation of macroautophagy by Leucine Rich Repeat Kinase 2 via Beclin-1. Sci Rep (2016) 0.78

Leucine-rich repeat kinase 2 interacts with p21-activated kinase 6 to control neurite complexity in mammalian brain. J Neurochem (2015) 0.77

ERKed by LRRK2: a cell biological perspective on hereditary and sporadic Parkinson's disease. Biochim Biophys Acta (2013) 0.76

LRRK2 Kinase Inhibition as a Therapeutic Strategy for Parkinson's Disease, Where Do We Stand? Curr Neuropharmacol (2016) 0.76

LRRK2 at the interface of autophagosomes, endosomes and lysosomes. Mol Neurodegener (2016) 0.76

Dysregulation of autophagy and mitochondrial function in Parkinson's disease. Transl Neurodegener (2016) 0.75

The LRRK2-macroautophagy axis and its relevance to Parkinson's disease. Biochem Soc Trans (2017) 0.75

Prelysosomal Compartments in the Unconventional Secretion of Amyloidogenic Seeds. Int J Mol Sci (2017) 0.75

Autophagy in the pathogenesis of ankylosing spondylitis. Clin Rheumatol (2016) 0.75

Fibroblast Biomarkers of Sporadic Parkinson's Disease and LRRK2 Kinase Inhibition. Mol Neurobiol (2015) 0.75

Articles cited by this

Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet (2008) 30.20

Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet (2009) 14.06

Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet (2011) 9.10

Genomewide association study of leprosy. N Engl J Med (2009) 8.17

Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci U S A (2005) 6.98

Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiol Dis (2006) 5.96

Kinase activity of mutant LRRK2 mediates neuronal toxicity. Nat Neurosci (2006) 5.32

Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease. Nat Med (2010) 4.45

Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells. J Neurochem (2008) 3.86

Neutral red uptake assay for the estimation of cell viability/cytotoxicity. Nat Protoc (2008) 3.76

The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. 'Protein modifications: beyond the usual suspects' review series. EMBO Rep (2008) 3.52

Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila. EMBO J (2008) 3.51

Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study. Lancet Neurol (2011) 3.36

The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease. Nat Rev Neurosci (2010) 3.14

Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. Autophagy (2010) 2.91

Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2. Nat Chem Biol (2011) 2.91

Leucine-rich repeat kinase 2 mutations and Parkinson's disease: three questions. ASN Neuro (2009) 2.85

LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum Mol Genet (2009) 2.55

The R1441C mutation of LRRK2 disrupts GTP hydrolysis. Biochem Biophys Res Commun (2007) 2.42

Leucine-rich repeat kinase 2 (LRRK2)/PARK8 possesses GTPase activity that is altered in familial Parkinson's disease R1441C/G mutants. J Neurochem (2007) 2.40

It takes two to tango: regulation of G proteins by dimerization. Nat Rev Mol Cell Biol (2009) 2.34

Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of alpha-synuclein, and apoptotic cell death in aged mice. Proc Natl Acad Sci U S A (2010) 2.34

Therapeutic targets in cancer cell metabolism and autophagy. Nat Biotechnol (2012) 2.27

p62 Targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding. J Cell Biol (2011) 2.16

Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2. PLoS One (2011) 1.93

LRRK2 is involved in the IFN-gamma response and host response to pathogens. J Immunol (2010) 1.85

Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson's disease. EMBO Mol Med (2012) 1.75

Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP. Hum Mol Genet (2011) 1.68

GTPase activity plays a key role in the pathobiology of LRRK2. PLoS Genet (2010) 1.63

LRRK2 inhibition attenuates microglial inflammatory responses. J Neurosci (2012) 1.61

Autophosphorylation in the leucine-rich repeat kinase 2 (LRRK2) GTPase domain modifies kinase and GTP-binding activities. J Mol Biol (2011) 1.42

The Parkinson's disease associated LRRK2 exhibits weaker in vitro phosphorylation of 4E-BP compared to autophosphorylation. PLoS One (2010) 1.39

Protein misfolding disorders and macroautophagy. Curr Opin Cell Biol (2010) 1.36

Parkinson's disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures. J Neural Transm (Vienna) (2011) 1.35

Loss of leucine-rich repeat kinase 2 causes age-dependent bi-phasic alterations of the autophagy pathway. Mol Neurodegener (2012) 1.34

Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant. J Neurochem (2011) 1.33

Propagation of human tumors in antithymocyte serum-treated mice. J Natl Cancer Inst (1974) 1.31

Chemoproteomics-based design of potent LRRK2-selective lead compounds that attenuate Parkinson's disease-related toxicity in human neurons. ACS Chem Biol (2011) 1.29

Impaired inflammatory responses in murine Lrrk2-knockdown brain microglia. PLoS One (2012) 1.21

LRRK2 kinase activity is dependent on LRRK2 GTP binding capacity but independent of LRRK2 GTP binding. PLoS One (2011) 1.19

GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent-N-arylbenzamide LRRK2 kinase inhibitor. Bioorg Med Chem Lett (2012) 1.16

Is inhibition of kinase activity the only therapeutic strategy for LRRK2-associated Parkinson's disease? BMC Med (2012) 1.10

CLIC1 function is required for beta-amyloid-induced generation of reactive oxygen species by microglia. J Neurosci (2008) 1.09

The function of ROCO proteins in health and disease. Biol Cell (2009) 1.09

LRRK2 and human disease: a complicated question or a question of complexes? Sci Signal (2012) 1.02

Phosphorylation of 4E-BP1 in the mammalian brain is not altered by LRRK2 expression or pathogenic mutations. PLoS One (2012) 0.99

The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway. Cell Mol Life Sci (2012) 0.99

Leprosy susceptibility: genetic variations regulate innate and adaptive immunity, and disease outcome. Future Microbiol (2011) 0.94

Identification of uncommon chromosomal aberrations in the neuroglioma cell line H4 by spectral karyotyping. J Neurooncol (2001) 0.90

Role of LRRK2 kinase activity in the pathogenesis of Parkinson's disease. Biochem Soc Trans (2012) 0.85

LRRK2 and autophagy: a common pathway for disease. Biochem Soc Trans (2012) 0.80

Parkinson disease, cancer, and LRRK2: causation or association? Neurology (2012) 0.80

Functional consequences of mutations in the autophagy genes in the pathogenesis of Crohn's disease. Inflamm Bowel Dis (2011) 0.78