Is inhibition of kinase activity the only therapeutic strategy for LRRK2-associated Parkinson's disease?

[1]  Houeto Jean-Luc.  [Parkinson's disease]. , 2022, La Revue du praticien.

[2]  Mindy I. Davis,et al.  Comprehensive analysis of kinase inhibitor selectivity , 2011, Nature Biotechnology.

[3]  G. Drewes,et al.  Chemoproteomics-based design of potent LRRK2-selective lead compounds that attenuate Parkinson's disease-related toxicity in human neurons. , 2011, ACS chemical biology.

[4]  A. West,et al.  Autophosphorylation in the leucine-rich repeat kinase 2 (LRRK2) GTPase domain modifies kinase and GTP-binding activities. , 2011, Journal of molecular biology.

[5]  Michael K. Hutchinson,et al.  Translation initiator EIF4G1 mutations in familial Parkinson disease. , 2011, American journal of human genetics.

[6]  M. Cookson,et al.  LRRK2 Kinase Activity Is Dependent on LRRK2 GTP Binding Capacity but Independent of LRRK2 GTP Binding , 2011, PloS one.

[7]  C. Schnell,et al.  LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice , 2011, Human molecular genetics.

[8]  B. Oostra,et al.  The LRRK2 R1441C mutation is more frequent than G2019S in Parkinson's disease patients from Southern Italy , 2011, Movement disorders : official journal of the Movement Disorder Society.

[9]  T. Dawson,et al.  Inhibitors of LRRK2 kinase attenuate neurodegeneration and Parkinson-like phenotypes in Caenorhabditis elegans and Drosophila Parkinson's disease models. , 2011, Human molecular genetics.

[10]  D. Hernandez,et al.  Genome-wide association study confirms extant PD risk loci among the Dutch , 2011, European Journal of Human Genetics.

[11]  W. Seol,et al.  Identification of chemicals to inhibit the kinase activity of leucine-rich repeat kinase 2 (LRRK2), a Parkinson's disease-associated protein. , 2011, Bioorganic & medicinal chemistry letters.

[12]  J. Jankovic,et al.  The association between Parkinson's disease and melanoma , 2011, International journal of cancer.

[13]  Dejun Yang,et al.  Models for LRRK2-Linked Parkinsonism , 2011, Parkinson's disease.

[14]  Y. Liu,et al.  Dopaminergic Neuronal Loss, Reduced Neurite Complexity and Autophagic Abnormalities in Transgenic Mice Expressing G2019S Mutant LRRK2 , 2011, PloS one.

[15]  B. Wolozin,et al.  Rac1 Protein Rescues Neurite Retraction Caused by G2019S Leucine-rich Repeat Kinase 2 (LRRK2)* , 2011, The Journal of Biological Chemistry.

[16]  N. Gray,et al.  Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2 , 2011, Nature chemical biology.

[17]  F. Gage,et al.  Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice , 2011, Neurobiology of Disease.

[18]  Miguel Ángel Martínez,et al.  Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies , 2011, The Lancet.

[19]  M. Vidailhet,et al.  Genome-wide association study confirms BST1 and suggests a locus on 12q24 as the risk loci for Parkinson's disease in the European population. , 2011, Human molecular genetics.

[20]  P. Aebischer,et al.  A Rat Model of Progressive Nigral Neurodegeneration Induced by the Parkinson's Disease-Associated G2019S Mutation in LRRK2 , 2011, The Journal of Neuroscience.

[21]  V. Baekelandt,et al.  Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant , 2011, Journal of neurochemistry.

[22]  Mark R. Cookson,et al.  The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease , 2010, Nature Reviews Neuroscience.

[23]  M. S. Luciano,et al.  LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease , 2010, Movement disorders : official journal of the Movement Disorder Society.

[24]  Nir London,et al.  Can self‐inhibitory peptides be derived from the interfaces of globular protein–protein interactions? , 2010, Proteins.

[25]  J. Nutt,et al.  Novel pathogenic LRRK2 p.Asn1437His substitution in familial Parkinson's disease , 2010, Movement disorders : official journal of the Movement Disorder Society.

[26]  C. Chien,et al.  LRRK2 G2019S Mutation Induces Dendrite Degeneration through Mislocalization and Phosphorylation of Tau by Recruiting Autoactivated GSK3β , 2010, The Journal of Neuroscience.

[27]  J. Vance,et al.  Gene-environment interactions in Parkinson's disease and other forms of parkinsonism. , 2010, Neurotoxicology.

[28]  A. Reith,et al.  Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser910/Ser935, disruption of 14-3-3 binding and altered cytoplasmic localization , 2010, The Biochemical journal.

[29]  J. Nutt,et al.  Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease , 2010, Nature Genetics.

[30]  A. Prescott,et al.  14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization , 2010, The Biochemical journal.

[31]  R. J. Kelleher,et al.  Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of α-synuclein, and apoptotic cell death in aged mice , 2010, Proceedings of the National Academy of Sciences.

[32]  Yichin Liu,et al.  Differential effects of divalent manganese and magnesium on the kinase activity of leucine-rich repeat kinase 2 (LRRK2). , 2010, Biochemistry.

[33]  M. Glicksman,et al.  Kinetic mechanistic studies of wild-type leucine-rich repeat kinase 2: characterization of the kinase and GTPase activities. , 2010, Biochemistry.

[34]  Eden R Martin,et al.  Genome‐Wide Association Study Confirms SNPs in SNCA and the MAPT Region as Common Risk Factors for Parkinson Disease , 2010, Annals of human genetics.

[35]  M. Cookson,et al.  The Parkinson's Disease Associated LRRK2 Exhibits Weaker In Vitro Phosphorylation of 4E-BP Compared to Autophosphorylation , 2010, PloS one.

[36]  M. Cookson,et al.  The R1441C mutation alters the folding properties of the ROC domain of LRRK2. , 2009, Biochimica et biophysica acta.

[37]  Z. Wszolek,et al.  Clinical features of LRRK2 parkinsonism. , 2009, Parkinsonism & related disorders.

[38]  Yusuke Nakamura,et al.  Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease , 2009, Nature Genetics.

[39]  Sonja W. Scholz,et al.  Genome-Wide Association Study reveals genetic risk underlying Parkinson’s disease , 2009, Nature Genetics.

[40]  A. Whitworth,et al.  Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss , 2009, Nature Neuroscience.

[41]  Aj Lees,et al.  Parkinson's disease (vol 373, pg 2055, 2009) , 2009 .

[42]  A. Wittinghofer,et al.  It takes two to tango: regulation of G proteins by dimerization , 2009, Nature Reviews Molecular Cell Biology.

[43]  I. Mata,et al.  LRRK2 mutations in patients with Parkinson's disease from Peru and Uruguay. , 2009, Parkinsonism & related disorders.

[44]  Z. Wszolek,et al.  Familial parkinsonism: study of original Sagamihara PARK8 (I2020T) kindred with variable clinicopathologic outcomes. , 2009, Parkinsonism & related disorders.

[45]  J. Jankovic,et al.  Lrrk2 R1441G-related Parkinson’s disease: evidence of a common founding event in the seventh century in Northern Spain , 2009, neurogenetics.

[46]  S. Eimer,et al.  Caenorhabditits elegans LRK-1 and PINK-1 Act Antagonistically in Stress Response and Neurite Outgrowth* , 2009, The Journal of Biological Chemistry.

[47]  B. Giasson,et al.  Identification of compounds that inhibit the kinase activity of leucine-rich repeat kinase 2. , 2009, Biochemical and biophysical research communications.

[48]  E. Brown,et al.  Investigation of leucine‐rich repeat kinase 2 , 2009, The FEBS journal.

[49]  M. Cookson,et al.  Leucine-rich repeat kinase 2 mutations and Parkinson’s disease: three questions , 2009, ASN neuro.

[50]  R. Takahashi,et al.  Phosphorylation of 4E‐BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila , 2008, The EMBO journal.

[51]  P. Matthews,et al.  LRRK2 Gly2019Ser penetrance in Arab–Berber patients from Tunisia: a case-control genetic study , 2008, The Lancet Neurology.

[52]  V. Mylius,et al.  The prevalence of the G2019S and R1441C/G/H mutations in LRRK2 in German patients with Parkinson’s disease , 2008, European journal of neurology.

[53]  E. Tolosa,et al.  Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study , 2008, The Lancet Neurology.

[54]  C. Chu,et al.  Role of autophagy in G2019S‐LRRK2‐associated neurite shortening in differentiated SH‐SY5Y cells , 2008, Journal of neurochemistry.

[55]  P. Deyn,et al.  Founder mutation p.R1441C in the leucine-rich repeat kinase 2 gene in Belgian Parkinson's disease patients , 2008, European Journal of Human Genetics.

[56]  Yuliang Wu,et al.  Direct binding of α‐actinin enhances TRPP3 channel activity , 2007 .

[57]  C. Olanow,et al.  Leucine‐rich repeat kinase 2 (LRRK2)/PARK8 possesses GTPase activity that is altered in familial Parkinson’s disease R1441C/G mutants , 2007, Journal of neurochemistry.

[58]  Shu G. Chen,et al.  The Parkinson's disease-associated protein, leucine-rich repeat kinase 2 (LRRK2), is an authentic GTPase that stimulates kinase activity. , 2007, Experimental cell research.

[59]  R. Nichols,et al.  LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson's disease mutants affect kinase activity. , 2007, The Biochemical journal.

[60]  M. Cookson,et al.  The R1441C mutation of LRRK2 disrupts GTP hydrolysis. , 2007, Biochemical and biophysical research communications.

[61]  P. Barone,et al.  Apoptotic mechanisms in mutant LRRK2-mediated cell death. , 2007, Human molecular genetics.

[62]  T. Gasser,et al.  Independent occurrence of I2020T mutation in the kinase domain of the leucine rich repeat kinase 2 gene in Japanese and German Parkinson's disease families , 2007, Neuroscience Letters.

[63]  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.

[64]  A. Abeliovich,et al.  The Familial Parkinsonism Gene LRRK2 Regulates Neurite Process Morphology , 2006, Neuron.

[65]  C. Ross,et al.  Kinase activity of mutant LRRK2 mediates neuronal toxicity , 2006, Nature Neuroscience.

[66]  David W. Miller,et al.  Kinase activity is required for the toxic effects of mutant LRRK2/dardarin , 2006, Neurobiology of Disease.

[67]  A. Singleton,et al.  Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data. , 2005, Brain : a journal of neurology.

[68]  C. Ross,et al.  Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[69]  Kazuko Hasegawa,et al.  An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family , 2005, Annals of neurology.

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

[71]  Andrew Lees,et al.  Cloning of the Gene Containing Mutations that Cause PARK8-Linked Parkinson's Disease , 2004, Neuron.

[72]  G. Tiana,et al.  A folding inhibitor of the HIV‐1 protease , 2004, Proteins.

[73]  R. Uitti,et al.  German-Canadian family (family A) with parkinsonism, amyotrophy, and dementia - Longitudinal observations. , 1997, Parkinsonism & related disorders.

[74]  T. Dawson,et al.  Inhibitors of LRRK 2 kinase attenuate neurodegeneration and Parkinson-like phenotypes in Caenorhabditis elegans and Drosophila Parkinson ’ s disease models , 2011 .

[75]  M. Santos‐Reis,et al.  Competing interests , 2010 .