Kinase inhibition of G2019S-LRRK2 enhances autolysosome formation and function to reduce endogenous alpha-synuclein intracellular inclusions

[1]  J. Trojanowski,et al.  Alzheimer’s disease tau is a prominent pathology in LRRK2 Parkinson’s disease , 2019, Acta Neuropathologica Communications.

[2]  S. Ho,et al.  Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson disease: role for therapeutic activation of chaperone-mediated autophagy (CMA) , 2019, Autophagy.

[3]  V. Baekelandt,et al.  Inhibition of LRRK2 or Casein Kinase 1 Results in LRRK2 Protein Destabilization , 2018, Molecular Neurobiology.

[4]  T. Iwatsubo,et al.  LRRK2 and its substrate Rab GTPases are sequentially targeted onto stressed lysosomes and maintain their homeostasis , 2018, Proceedings of the National Academy of Sciences.

[5]  A. Cuervo,et al.  Selective autophagy as a potential therapeutic target for neurodegenerative disorders , 2018, The Lancet Neurology.

[6]  A. Hicks,et al.  A new hypothesis for Parkinson’s disease pathogenesis: GTPase-p38 MAPK signaling and autophagy as convergence points of etiology and genomics , 2018, Molecular Neurodegeneration.

[7]  A. Stepan,et al.  LRRK2 activation in idiopathic Parkinson’s disease , 2018, Science Translational Medicine.

[8]  Xingdong Zhou,et al.  Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion , 2018, Autophagy.

[9]  M. Cookson,et al.  Detection of endogenous S1292 LRRK2 autophosphorylation in mouse tissue as a readout for kinase activity. , 2018, NPJ Parkinson's disease.

[10]  J. Hardy,et al.  mTOR independent alteration in ULK1 Ser758 phosphorylation following chronic LRRK2 kinase inhibition , 2018, Bioscience reports.

[11]  J. Schapansky,et al.  Familial knockin mutation of LRRK2 causes lysosomal dysfunction and accumulation of endogenous insoluble α-synuclein in neurons , 2018, Neurobiology of Disease.

[12]  N. Hattori,et al.  Loss of autophagy in dopaminergic neurons causes Lewy pathology and motor dysfunction in aged mice , 2018, Scientific Reports.

[13]  M. Cookson,et al.  LRRK2 phosphorylates membrane-bound Rabs and is activated by GTP-bound Rab7L1 to promote recruitment to the trans-Golgi network , 2018, Human molecular genetics.

[14]  Matthias Mann,et al.  Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis , 2017, eLife.

[15]  A. Meléndez,et al.  The recycling endosome protein RAB-10 promotes autophagic flux and localization of the transmembrane protein ATG-9 , 2017, Autophagy.

[16]  A. Hicks,et al.  CADPS2 gene expression is oppositely regulated by LRRK2 and alpha-synuclein. , 2017, Biochemical and biophysical research communications.

[17]  A. West,et al.  LRRK2 Antisense Oligonucleotides Ameliorate α-Synuclein Inclusion Formation in a Parkinson’s Disease Mouse Model , 2017, Molecular therapy. Nucleic acids.

[18]  N. Hattori,et al.  Vps35 in cooperation with LRRK2 regulates synaptic vesicle endocytosis through the endosomal pathway in Drosophila , 2017, Human molecular genetics.

[19]  J. Hopwood,et al.  Endo‐lysosomal and autophagic dysfunction: a driving factor in Alzheimer's disease? , 2017, Journal of neurochemistry.

[20]  M. Volta,et al.  LRRK2 mouse models: dissecting the behavior, striatal neurochemistry and neurophysiology of PD pathogenesis. , 2017, Biochemical Society transactions.

[21]  D. James Surmeier,et al.  Selective neuronal vulnerability in Parkinson disease , 2017, Nature Reviews Neuroscience.

[22]  M. Cookson.  Cellular functions of LRRK2 implicate vesicular trafficking pathways in Parkinson's disease. , 2016, Biochemical Society transactions.

[23]  D. James,et al.  A novel Rab10-EHBP1-EHD2 complex essential for the autophagic engulfment of lipid droplets , 2016, Science Advances.

[24]  N. Dzamko,et al.  LRRK2 inhibitors and their potential in the treatment of Parkinson’s disease: current perspectives , 2016, Clinical pharmacology : advances and applications.

[25]  Andrew B West,et al.  G2019S-LRRK2 Expression Augments α-Synuclein Sequestration into Inclusions in Neurons , 2016, The Journal of Neuroscience.

[26]  Matthias Mann,et al.  Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases , 2016, eLife.

[27]  A. Milnerwood,et al.  Insights from late-onset familial parkinsonism on the pathogenesis of idiopathic Parkinson's disease , 2015, The Lancet Neurology.

[28]  Elie Needle,et al.  Pathogenic LRRK2 mutations, through increased kinase activity, produce enlarged lysosomes with reduced degradative capacity and increase ATP13A2 expression. , 2015, Human molecular genetics.

[29]  Elie Needle,et al.  Leucine-rich Repeat Kinase 2 (LRRK2) Pharmacological Inhibition Abates α-Synuclein Gene-induced Neurodegeneration* , 2015, The Journal of Biological Chemistry.

[30]  Mark R Cookson,et al.  LRRK2 Pathways Leading to Neurodegeneration , 2015, Current Neurology and Neuroscience Reports.

[31]  A. Cuervo,et al.  Methods to study chaperone-mediated autophagy. , 2015, Methods.

[32]  D. Ehrnhoefer,et al.  Autophagy in Huntington disease and huntingtin in autophagy , 2015, Trends in Neurosciences.

[33]  A. Schapira,et al.  Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition , 2015, Journal of Cell Science.

[34]  A. West.  Ten Years and Counting: Moving Leucine-Rich Repeat Kinase 2 Inhibitors to the Clinic , 2014, Movement disorders : official journal of the Movement Disorder Society.

[35]  N. Kuhlmann,et al.  Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice , 2014, Front. Cell. Neurosci..

[36]  J. Schapansky,et al.  Membrane recruitment of endogenous LRRK2 precedes its potent regulation of autophagy. , 2014, Human molecular genetics.

[37]  F. J. Romero,et al.  The LRRK2 inhibitor GSK2578215A induces protective autophagy in SH-SY5Y cells: involvement of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS signaling , 2014, Cell Death and Disease.

[38]  I. Ferrer,et al.  LRRK2 delays degradative receptor trafficking by impeding late endosomal budding through decreasing Rab7 activity. , 2014, Human molecular genetics.

[39]  A. West,et al.  Abrogation of α-synuclein–mediated dopaminergic neurodegeneration in LRRK2-deficient rats , 2014, Proceedings of the National Academy of Sciences.

[40]  V. Baekelandt,et al.  In silico, in vitro and cellular analysis with a kinome-wide inhibitor panel correlates cellular LRRK2 dephosphorylation to inhibitor activity on LRRK2 , 2014, Front. Mol. Neurosci..

[41]  Kenichi Yoshida,et al.  Detection of WIPI1 mRNA as an indicator of autophagosome formation , 2014, Autophagy.

[42]  Suneil K. Kalia,et al.  Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease , 2014, Proceedings of the National Academy of Sciences.

[43]  Michael J. Devine,et al.  Pathogenic Parkinson’s disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation☆ , 2013, Biochemical and biophysical research communications.

[44]  Andy H. Choi,et al.  Current Perspectives , 2013, Journal of dental research.

[45]  M. Farrer,et al.  Advances in the genetics of Parkinson disease , 2013, Nature Reviews Neurology.

[46]  A. Consiglio,et al.  Interplay of LRRK2 with chaperone-mediated autophagy , 2013, Nature Neuroscience.

[47]  K. Marder,et al.  RAB7L1 Interacts with LRRK2 to Modify Intraneuronal Protein Sorting and Parkinson’s Disease Risk , 2013, Neuron.

[48]  Sangeeta Khare,et al.  Guidelines for the use and interpretation of assays formonitoring autophagy (3rd edition) , 2016 .

[49]  D. Klionsky,et al.  The role of autophagy in Parkinson's disease. , 2012, Cold Spring Harbor perspectives in medicine.

[50]  G. Churchill,et al.  Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP , 2011, Human molecular genetics.

[51]  R. Eils,et al.  Concurrent detection of autolysosome formation and lysosomal degradation by flow cytometry in a high-content screen for inducers of autophagy , 2011, BMC Biology.

[52]  M. Vila,et al.  Pathogenic Lysosomal Depletion in Parkinson's Disease , 2010, The Journal of Neuroscience.

[53]  Richard C. Wang,et al.  Autophagy in cellular growth control , 2010, FEBS letters.

[54]  J. Trojanowski,et al.  Exogenous α-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells , 2009, Proceedings of the National Academy of Sciences.

[55]  Richard Wade-Martins,et al.  LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. , 2009, Human molecular genetics.

[56]  H. Qing,et al.  Lrrk2 phosphorylates alpha synuclein at serine 129: Parkinson disease implications. , 2009, Biochemical and biophysical research communications.

[57]  C. Warren Olanow,et al.  Alterations in lysosomal and proteasomal markers in Parkinson's disease: Relationship to alpha-synuclein inclusions , 2009, Neurobiology of Disease.

[58]  R A Knight,et al.  Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes , 2009, Cell Death and Differentiation.

[59]  A. Cuervo,et al.  Constitutive activation of chaperone-mediated autophagy in cells with impaired macroautophagy. , 2008, Molecular biology of the cell.

[60]  A. Cuervo,et al.  Autophagy and neurodegeneration: when the cleaning crew goes on strike , 2007, The Lancet Neurology.

[61]  K. Lim,et al.  Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. , 2007, Human molecular genetics.

[62]  Masaaki Komatsu,et al.  Loss of autophagy in the central nervous system causes neurodegeneration in mice , 2006, Nature.

[63]  Thomas Meitinger,et al.  Mutations in LRRK2 Cause Autosomal-Dominant Parkinsonism with Pleomorphic Pathology , 2004, Neuron.

[64]  Peter T. Lansbury,et al.  Impaired Degradation of Mutant α-Synuclein by Chaperone-Mediated Autophagy , 2004, Science.

[65]  R. North,et al.  T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor , 1980, The Journal of experimental medicine.

[66]  L. Frost,et al.  The Use of DQ-BSA to Monitor the Turnover of Autophagy-Associated Cargo. , 2017, Methods in enzymology.

[67]  C. Manzoni,et al.  LRRK2 and Autophagy. , 2017, Advances in neurobiology.

[68]  J. Trojanowski,et al.  Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease. , 2015, JAMA neurology.

[69]  J. M. Bravo-San Pedro,et al.  The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway , 2012, Cellular and Molecular Life Sciences.

[70]  Leonidas Stefanis,et al.  Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. , 2004, Science.