Pharmacological LRRK2 kinase inhibition induces LRRK2 protein destabilization and proteasomal degradation

LRRK2 Kinase Inhibition as a Therapeutic Strategy for Parkinson's Disease, Where Do We Stand?

(2016) Jean-Marc Taymans et al.   Current Neuropharmacology

LRRK2 dephosphorylation increases its ubiquitination

(2015) Jing Zhao et al.   BIOCHEMICAL JOURNAL

Effect of selective LRRK2 kinase inhibition on nonhuman primate lung

(2015) Reina N. Fuji et al.   Science Translational Medicine

Leucine-rich repeat kinase 2 inhibitors: a review of recent patents (2011 – 2013)

(2014) Raghava R Kethiri et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Discovery and Preclinical Profiling of 3-[4-(Morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile (PF-06447475), a Highly Potent, Selective, Brain Penetrant, and in Vivo Active LRRK2 Kinase Inhibitor

(2014) Jaclyn L. Henderson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Mutant LRRK2 Toxicity in Neurons Depends on LRRK2 Levels and Synuclein But Not Kinase Activity or Inclusion Bodies

(2014) G. Skibinski et al.   JOURNAL OF NEUROSCIENCE

Surfactant Secretion in LRRK2 Knock-Out Rats: Changes in Lamellar Body Morphology and Rate of Exocytosis

(2014) Pika Miklavc et al.   PLoS One

Lack of Correlation between the Kinase Activity of LRRK2 Harboring Kinase-Modifying Mutations and Its Phosphorylation at Ser910, 935, and Ser955

(2014) Genta Ito et al.   PLoS One

Abrogation of  -synuclein-mediated dopaminergic neurodegeneration in LRRK2-deficient rats

(2014) J. P. L. Daher et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Phosphorylation of LRRK2 by casein kinase 1α regulates trans-Golgi clustering via differential interaction with ARHGEF7

(2014) Ruth Chia et al.   Nature Communications

In silico, in vitro and cellular analysis with a kinome-wide inhibitor panel correlates cellular LRRK2 dephosphorylation to inhibitor activity on LRRK2

(2014) Renée Vancraenenbroeck et al.   Frontiers in Molecular Neuroscience

LRRK2 kinase activity and biology are not uniformly predicted by its autophosphorylation and cellular phosphorylation site status

(2014) April Reynolds et al.   Frontiers in Molecular Neuroscience

Phosphatases of α-synuclein, LRRK2, and tau: important players in the phosphorylation-dependent pathology of Parkinsonism

(2014) Jean-Marc Taymans et al.   Frontiers in Genetics

Identification of protein phosphatase 1 as a regulator of the LRRK2 phosphorylation cycle

(2013) Evy Lobbestael et al.   BIOCHEMICAL JOURNAL

Evidence that the LRRK2 ROC domain Parkinson's disease-associated mutants A1442P and R1441C exhibit increased intracellular degradation

(2013) Izabella D. Greene et al.   JOURNAL OF NEUROSCIENCE RESEARCH

Loss of Leucine-Rich Repeat Kinase 2 (LRRK2) in Rats Leads to Progressive Abnormal Phenotypes in Peripheral Organs

(2013) Marco A. S. Baptista et al.   PLoS One

Parkinson-related LRRK2 mutation R1441C/G/H impairs PKA phosphorylation of LRRK2 and disrupts its interaction with 14-3-3

(2013) K. Muda et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Phosphorylation of LRRK2: from kinase to substrate

(2012) Evy Lobbestael et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

GSK2578215A; A potent and highly selective 2-arylmethyloxy-5-substitutent-N-arylbenzamide LRRK2 kinase inhibitor

(2012) Alastair D. Reith et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Characterization of TAE684 as a potent LRRK2 kinase inhibitor

(2012) Jinwei Zhang et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Leucine-rich repeat kinase 2 inhibitors: a patent review (2006 – 2011)

(2012) Xianming Deng et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Kinase inhibitors arrest neurodegeneration in cell and C. elegans models of LRRK2 toxicity

(2012) C. Yao et al.   HUMAN MOLECULAR GENETICS

Development of an enzyme-linked immunosorbent assay for detection of cellular and in vivo LRRK2 S935 phosphorylation

(2012) Lore Delbroek et al.   JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Loss of leucine-rich repeat kinase 2 causes age-dependent bi-phasic alterations of the autophagy pathway

(2012) Youren Tong et al.   Molecular Neurodegeneration

The IkappaB Kinase Family Phosphorylates the Parkinson’s Disease Kinase LRRK2 at Ser935 and Ser910 during Toll-Like Receptor Signaling

(2012) Nicolas Dzamko et al.   PLoS One

Screening for Novel LRRK2 Inhibitors Using a High-Throughput TR-FRET Cellular Assay for LRRK2 Ser935 Phosphorylation

(2012) Spencer B. Hermanson et al.   PLoS One

Ser1292 Autophosphorylation Is an Indicator of LRRK2 Kinase Activity and Contributes to the Cellular Effects of PD Mutations

(2012) Z. Sheng et al.   Science Translational Medicine

Pharmacological Rescue of Mitochondrial Deficits in iPSC-Derived Neural Cells from Patients with Familial Parkinson's Disease

(2012) O. Cooper et al.   Science Translational Medicine

Brain Penetrant LRRK2 Inhibitor

(2012) Hwan Geun Choi et al.   ACS Medicinal Chemistry Letters

Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database

(2012) Christina M. Lill et al.   PLoS Genetics

Chemoproteomics-Based Design of Potent LRRK2-Selective Lead Compounds That Attenuate Parkinson’s Disease-Related Toxicity in Human Neurons

(2011) Nigel Ramsden et al.   ACS Chemical Biology

LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice

(2011) Martin C. Herzig et al.   HUMAN MOLECULAR GENETICS

Phosphorylation of LRRK2 serines 955 and 973 is disrupted by Parkinson’s disease mutations and LRRK2 pharmacological inhibition

(2011) Elizabeth A. Doggett et al.   JOURNAL OF NEUROCHEMISTRY

Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case–control study

(2011) Owen A Ross et al.   LANCET NEUROLOGY

Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2

(2011) Xianming Deng et al.   Nature Chemical Biology

Phosphorylation-Dependent 14-3-3 Binding to LRRK2 Is Impaired by Common Mutations of Familial Parkinson's Disease

(2011) Xianting Li et al.   PLoS One

Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser910/Ser935, disruption of 14-3-3 binding and altered cytoplasmic localization

(2010) Nicolas Dzamko et al.   BIOCHEMICAL JOURNAL

14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization

(2010) R. Jeremy Nichols et al.   BIOCHEMICAL JOURNAL

Phosphopeptide Analysis Reveals Two Discrete Clusters of Phosphorylation in the N-Terminus and the Roc Domain of the Parkinson-Disease Associated Protein Kinase LRRK2

(2010) Christian Johannes Gloeckner et al.   JOURNAL OF PROTEOME RESEARCH

Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease

(2010) Byoung Dae Lee et al.   NATURE MEDICINE

Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of  -synuclein, and apoptotic cell death in aged mice

(2010) Y. Tong et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Leucine-Rich Repeat Kinase 2 Mutations and Parkinson's Disease: Three Questions

(2009) Elisa Greggio et al.   ASN Neuro

Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in Parkinson's disease

(2009) R. Jeremy Nichols et al.   BIOCHEMICAL JOURNAL

Molecular pathogenesis of Parkinson disease: insights from genetic studies

(2009) Thomas Gasser   EXPERT REVIEWS IN MOLECULAR MEDICINE

LRRK2gene variation and its contribution to Parkinson disease

(2009) Coro Paisán-Ruiz   HUMAN MUTATION

Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease

(2009) Wataru Satake et al.   NATURE GENETICS

Genome-wide association study reveals genetic risk underlying Parkinson's disease

(2009) Javier Simón-Sánchez et al.   NATURE GENETICS

Leucine-Rich Repeat Kinase 2 Regulates the Progression of Neuropathology Induced by Parkinson's-Disease-Related Mutant α-synuclein

(2009) Xian Lin et al.   NEURON

CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity

(2009) Han Seok Ko et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The Chaperone Activity of Heat Shock Protein 90 Is Critical for Maintaining the Stability of Leucine-Rich Repeat Kinase 2

(2008) L. Wang et al.   JOURNAL OF NEUROSCIENCE