Kinases and kinase signaling pathways: Potential therapeutic targets in Parkinson's disease

Progress in Neurobiology - Tập 98 - Trang 207-221 - 2012
Gang Wang1, Jing Pan1, Sheng-Di Chen1,2
1Department of Neurology & Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
2Lab of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes of Biological Sciences (SIBS), Chinese Academy of Science (CAS) & Shanghai Jiao Tong University School of Medicine, Shanghai, China

Tài liệu tham khảo

Abdalla-Carvalho, 2010, Genetic analysis of LRRK2 functional domains in Brazilian patients with Parkinson's disease, European Journal of Neurology, 17, 1479, 10.1111/j.1468-1331.2010.03039.x Abeliovich, 2007, Parkinson's disease: pro-survival effects of PINK1, Nature, 448, 759, 10.1038/448759a Abou-Sleiman, 2006, A heterozygous effect for PINK1 mutations in Parkinson's disease?, Annals of Neurology, 60, 414, 10.1002/ana.20960 Akundi, 2011, Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice, PLoS One, 6, e16038, 10.1371/journal.pone.0016038 Akundi, 2012, PINK1 enhances insulin-like growth factor-1-dependent Akt signaling and protection against apoptosis, Neurobiology of Disease, 45, 469, 10.1016/j.nbd.2011.08.034 Aleyasin, 2010, DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway, Proceedings of the National Academy of Sciences of the United States of America, 107, 3186, 10.1073/pnas.0914876107 Alnemri, 2007, HtrA2 and Parkinson's disease: think PINK?, Nature Cell Biology, 9, 1227, 10.1038/ncb1107-1227 Amin, 2002, Cyclin-dependent kinase 5 (cdk5) activation requires interaction with three domains of p35, Journal of Neuroscience Research, 67, 354, 10.1002/jnr.10116 Benamer, 2010, LRRK2 G2019S in the North African population: a review, European Neurology, 63, 321, 10.1159/000279653 Berwick, 2011, LRRK2 signaling pathways: the key to unlocking neurodegeneration?, Trends in Cell Biology, 21, 257, 10.1016/j.tcb.2011.01.001 Bishop, 2010, Hyperexcitable substantia nigra dopamine neurons in PINK1- and HtrA2/Omi-deficient mice, Journal of Neurophysiology, 104, 3009, 10.1152/jn.00466.2010 Biskup, 2006, Localization of LRRK2 to membranous and vesicular structures in mammalian brain, Annals of Neurology, 60, 557, 10.1002/ana.21019 Bonifati, 2010, Shaking the genome: new studies reveal genetic risk for Parkinson's disease, The Lancet Neurology, 9, 136, 10.1016/S1474-4422(09)70363-1 Bonifati, 2012, Autosomal recessive parkinsonism, Parkinsonism & Related Disorders, 18, S4, 10.1016/S1353-8020(11)70004-9 Borsello, 2007, JNK signalling: a possible target to prevent neurodegeneration, Current Pharmaceutical Design, 13, 1875, 10.2174/138161207780858384 Braak, 2004, Stages in the development of Parkinson's disease-related pathology, Cell and Tissue Research, 318, 121, 10.1007/s00441-004-0956-9 Braithwaite, 2012, alpha-Synuclein phosphorylation as a therapeutic target in Parkinson's disease, Reviews in the Neurosciences, 23, 191, 10.1515/revneuro-2011-0067 Braithwaite, 2012, Targeting phosphatases as the next generation of disease modifying therapeutics for Parkinson's disease, Neurochemistry International, 10.1016/j.neuint.2012.01.031 Brambilla, 2003, Targeting Ras/ERK signaling in the striatum: will it help?, Molecular Psychiatry, 8, 366, 10.1038/sj.mp.4001291 Brion, 1995, Cortical and brainstem-type Lewy bodies are immunoreactive for the cyclin-dependent kinase 5, American Journal of Pathology, 147, 1465 Cali, 2011, Mitochondria, calcium, and endoplasmic reticulum stress in Parkinson's disease, Biofactors, 37, 228, 10.1002/biof.159 Camins, 2006, The role of CDK5/P25 formation/inhibition in neurodegeneration, Drug News & Perspectives, 19, 453, 10.1358/dnp.2006.19.8.1043961 Carballo-Carbajal, 2010, Leucine-rich repeat kinase 2 induces alpha-synuclein expression via the extracellular signal-regulated kinase pathway, Cellular Signalling, 22, 821, 10.1016/j.cellsig.2010.01.006 Cassarino, 2000, Interaction among mitochondria, mitogen-activated protein kinases, and nuclear factor-kappaB in cellular models of Parkinson's disease, Journal of Neurochemistry, 74, 1384, 10.1046/j.1471-4159.2000.0741384.x Chan, 2011, Rac1 protein rescues neurite retraction caused by G2019S leucine-rich repeat kinase 2 (LRRK2), The Journal of Biological Chemistry, 286, 16140, 10.1074/jbc.M111.234005 Cheng, 2011, Insulin-like growth factor-I mediates neuroprotection in proteasome inhibition-induced cytotoxicity in SH-SY5Y cells, Molecular and Cellular Neurosciences, 47, 181, 10.1016/j.mcn.2011.04.002 Cheng, 2008, Glycogen synthase kinase 3beta interacts with and phosphorylates the spindle-associated protein astrin, The Journal of Biological Chemistry, 283, 2454, 10.1074/jbc.M706794200 Chien, 2011, Impairment of oxidative stress-induced heme oxygenase-1 expression by the defect of Parkinson-related gene of PINK1, Journal of Neurochemistry, 117, 643 Choi, 2004, Phosphorylation of p38 MAPK induced by oxidative stress is linked to activation of both caspase-8- and -9-mediated apoptotic pathways in dopaminergic neurons, The Journal of Biological Chemistry, 279, 20451, 10.1074/jbc.M311164200 Cohen, 2001, The renaissance of GSK3, Nature Reviews. Molecular Cell Biology, 2, 769, 10.1038/35096075 Cole, 2006, Distinct priming kinases contribute to differential regulation of collapsin response mediator proteins by glycogen synthase kinase-3 in vivo, The Journal of Biological Chemistry, 281, 16591, 10.1074/jbc.M513344200 Conner, 2003, AAK1-mediated micro2 phosphorylation is stimulated by assembled clathrin, Traffic, 4, 885, 10.1046/j.1398-9219.2003.0142.x Cook, 2009, A critical evaluation of the ubiquitin–proteasome system in Parkinson's disease, Biochimica et Biophysica Acta, 1792, 664, 10.1016/j.bbadis.2009.01.012 Cookson, 2010, The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease, Nature Reviews Neuroscience, 11, 791, 10.1038/nrn2935 Cookson, 2007, The roles of kinases in familial Parkinson's disease, The Journal of Neuroscience, 27, 11865, 10.1523/JNEUROSCI.3695-07.2007 Cornejo Castro, 2010, Parkinson's disease-associated DJ-1 modulates innate immunity signaling in Caenorhabditis elegans, Journal of Neural Transmission, 117, 599, 10.1007/s00702-010-0397-4 Cuny, 2009, Kinase inhibitors as potential therapeutics for acute and chronic neurodegenerative conditions, Current Pharmaceutical Design, 15, 3919, 10.2174/138161209789649330 Dagda, 2009, Mitochondrial kinases in Parkinson's disease: converging insights from neurotoxin and genetic models, Mitochondrion, 9, 289, 10.1016/j.mito.2009.06.001 Das Evcimen, 2007, The role of protein kinase C activation and the vascular complications of diabetes, Pharmacological Research, 55, 498, 10.1016/j.phrs.2007.04.016 Das, 2012, Role of tau kinases (CDK5R1 and GSK3B) in Parkinson's disease: a study from India, Neurobiology of Aging, 33, 1485.e9, 10.1016/j.neurobiolaging.2010.10.016 Deas, 2011, Mitophagy and Parkinson's disease: the PINK1-parkin link, Biochimica et Biophysica Acta, 1813, 623, 10.1016/j.bbamcr.2010.08.007 Demetrick, 1994, Chromosomal mapping of human CDK2, CDK4, and CDK5 cell cycle kinase genes, Cytogenetics and Cell Genetics, 66, 72, 10.1159/000133669 Deng, 2011, Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2, Nature Chemical Biology, 7, 203, 10.1038/nchembio.538 Duka, 2009, Alpha-Synuclein contributes to GSK-3beta-catalyzed Tau phosphorylation in Parkinson's disease models, The FASEB Journal, 23, 2820, 10.1096/fj.08-120410 Dumitriu, 2011, Cyclin-G-associated kinase modifies alpha-synuclein expression levels and toxicity in Parkinson's disease: results from the GenePD study, Human Molecular Genetics, 20, 1478, 10.1093/hmg/ddr026 Eggers, 2010, Progression of subtle motor signs in PINK1 mutation carriers with mild dopaminergic deficit, Neurology, 74, 1798, 10.1212/WNL.0b013e3181e0f79c Elstner, 2011, Expression analysis of dopaminergic neurons in Parkinson's disease and aging links transcriptional dysregulation of energy metabolism to cell death, Acta Neuropathologica, 122, 75, 10.1007/s00401-011-0828-9 Farghaian, 2011, Bioinformatic prediction and confirmation of beta-adducin as a novel substrate of glycogen synthase kinase 3, The Journal of Biological Chemistry, 286, 25274, 10.1074/jbc.M111.251629 Faris, 1998, Stress-induced Fas ligand expression in T cells is mediated through a MEK kinase 1-regulated response element in the Fas ligand promoter, Molecular and Cellular Biology, 18, 5414, 10.1128/MCB.18.9.5414 Fayard, 2010, Protein kinase B (PKB/Akt), a key mediator of the PI3K signaling pathway, Current Topics in Microbiology and Immunology, 346, 31 Fischer, 2003, Cdk5 in the adult non-demented brain, Current Drug Targets – CNS & Neurological Disorders, 2, 375, 10.2174/1568007033482706 Fritz, 2006, Rho GTPases: promising cellular targets for novel anticancer drugs, Current Cancer Drug Targets, 6, 1 Fu, 2009, The small GTPase activity of the ROC domain from LRRK2, a Parkinson's disease related protein, Protein and Peptide Letters, 16, 1442, 10.2174/092986609789839386 Fujioka, 2012, Update on Genetics of Parkinsonism, Neurodegenerative Diseases, 10, 257, 10.1159/000334285 Funayama, 2002, A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1, Annals of Neurology, 51, 296, 10.1002/ana.10113 Gallo, 2002, Mixed-lineage kinase control of JNK and p38 MAPK pathways, Nature Reviews. Molecular Cell Biology, 3, 663, 10.1038/nrm906 Gandhi, 2006, PINK1 protein in normal human brain and Parkinson's disease, Brain, 129, 1720, 10.1093/brain/awl114 Ghazavi, 2011, PRKN, DJ-1, and PINK1 screening identifies novel splice site mutation in PRKN and two novel DJ-1 mutations, Movement Disorders, 26, 80, 10.1002/mds.23417 Ghigo, 2010, PI3K inhibition in inflammation: toward tailored therapies for specific diseases, Bioessays, 32, 185, 10.1002/bies.200900150 Gloeckner, 2010, Phosphopeptide analysis reveals two discrete clusters of phosphorylation in the N-terminus and the Roc domain of the Parkinson-disease associated protein kinase LRRK2, Journal of Proteome Research, 9, 1738, 10.1021/pr9008578 Gloeckner, 2009, The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro, Journal of Neurochemistry, 109, 959, 10.1111/j.1471-4159.2009.06024.x Goold, 2001, Microtubule-associated protein 1B phosphorylation by glycogen synthase kinase 3beta is induced during PC12 cell differentiation, Journal of Cell Science, 114, 4273, 10.1242/jcs.114.23.4273 Greenamyre, 2004, Biomedicine. Parkinson's – divergent causes, convergent mechanisms, Science, 304, 1120, 10.1126/science.1098966 Greener, 2000, Role of cyclin G-associated kinase in uncoating clathrin-coated vesicles from non-neuronal cells, The Journal of Biological Chemistry, 275, 1365, 10.1074/jbc.275.2.1365 Greggio, 2006, Kinase activity is required for the toxic effects of mutant LRRK2/dardarin, Neurobiology of Disease, 23, 329, 10.1016/j.nbd.2006.04.001 Greggio, 2007, Kinase signaling pathways as potential targets in the treatment of Parkinson's disease, Expert Review of Proteomics, 4, 783, 10.1586/14789450.4.6.783 Guan, 2010, Effect of cdk5 antagonist on l-dopa-induced dyskinesias in a rat model of Parkinson's disease, The International Journal of Neuroscience, 120, 421, 10.3109/00207451003797694 Gu, 2009, Involvement of ERK1/2 signaling pathway in DJ-1-induced neuroprotection against oxidative stress, Biochemical and Biophysical Research Communications, 383, 469, 10.1016/j.bbrc.2009.04.037 Gu, 2008, Mu2 adaptin facilitates but is not essential for synaptic vesicle recycling in Caenorhabditis elegans, The Journal of Cell Biology, 183, 881, 10.1083/jcb.200806088 Harper, 2003, MAPKs: new targets for neurodegeneration, Expert Opinion on Therapeutic Targets, 7, 187, 10.1517/14728222.7.2.187 Hernandez, 2009, GSK3 inhibitors and disease, Mini Reviews in Medicinal Chemistry, 9, 1024, 10.2174/138955709788922647 Higashi, 2010, GIGYF2 is present in endosomal compartments in the mammalian brains and enhances IGF-1-induced ERK1/2 activation, Journal of Neurochemistry, 115, 423, 10.1111/j.1471-4159.2010.06930.x Honing, 2005, Phosphatidylinositol-(4,5)-bisphosphate regulates sorting signal recognition by the clathrin-associated adaptor complex AP2, Molecular Cell, 18, 519, 10.1016/j.molcel.2005.04.019 Ho, 2012, Mitochondrial neuronal uncoupling proteins: a target for potential disease-modification in Parkinson's disease, Translational Neurodegeneration, 1, 3, 10.1186/2047-9158-1-3 Hsu, 2010, MKK6 binds and regulates expression of Parkinson's disease-related protein LRRK2, Journal of Neurochemistry, 112, 1593, 10.1111/j.1471-4159.2010.06568.x Hsu, 2010, LRRK2 and the stress response: interaction with MKKs and JNK-interacting proteins, Neurodegenerative Diseases, 7, 68, 10.1159/000285509 Hwang, 2010, Parkin suppresses c-Jun N-terminal kinase-induced cell death via transcriptional regulation in Drosophila, Molecular Cell, 29, 575, 10.1007/s10059-010-0068-1 Infante, 2010, Synergistic effect of two oxidative stress-related genes (heme oxygenase-1 and GSK3beta) on the risk of Parkinson's disease, European Journal of Neurology, 17, 760, 10.1111/j.1468-1331.2009.02908.x Imai, 2008, Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila, The EMBO Journal, 27, 2432, 10.1038/emboj.2008.163 Jaleel, 2007, LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson's disease mutants affect kinase activity, The Biochemical Journal, 405, 307, 10.1042/BJ20070209 Jankowski, 2007, [The role of JNK pathway in familial Parkinson's disease], Postepy Biochemii, 53, 297 Jope, 2004, The glamour and gloom of glycogen synthase kinase-3, Trends in Biochemical Sciences, 29, 95, 10.1016/j.tibs.2003.12.004 Kaidanovich-Beilin, 2011, GSK-3: functional insights from cell biology and animal models, Frontiers in Molecular Neuroscience, 4, 40, 10.3389/fnmol.2011.00040 Kalinderi, 2011, GSK3beta polymorphisms, MAPT H1 haplotype and Parkinson's disease in a Greek cohort, Neurobiology of Aging, 32, e541 Kamikawaji, 2009, Identification of the autophosphorylation sites of LRRK2, Biochemistry, 48, 10963, 10.1021/bi9011379 Kanaoka, 1997, GAK: a cyclin G associated kinase contains a tensin/auxilin-like domain, FEBS Letters, 402, 73, 10.1016/S0014-5793(96)01484-6 Karunakaran, 2009, Activation of p38 MAPK in the substantia nigra leads to nuclear translocation of NF-kappaB in MPTP-treated mice: implication in Parkinson's disease, Journal of Neurochemistry, 109, 1791, 10.1111/j.1471-4159.2009.06112.x Karunakaran, 2008, Selective activation of p38 mitogen-activated protein kinase in dopaminergic neurons of substantia nigra leads to nuclear translocation of p53 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, The Journal of Neuroscience, 28, 12500, 10.1523/JNEUROSCI.4511-08.2008 Kawakami, 2011, Stimulatory effect of alpha-synuclein on the tau-phosphorylation by GSK-3beta, The FEBS Journal, 278, 4895, 10.1111/j.1742-4658.2011.08389.x Khan, 2005, Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data, Brain, 128, 2786, 10.1093/brain/awh667 Kim, 2001, Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1, Molecular and Cellular Biology, 21, 893, 10.1128/MCB.21.3.893-901.2001 Kim, 2002, Akt1 regulates a JNK scaffold during excitotoxic apoptosis, Neuron, 35, 697, 10.1016/S0896-6273(02)00821-8 Kim, 2011, Dopaminergic pathway reconstruction by Akt/Rheb-induced axon regeneration, Annals of Neurology, 70, 110, 10.1002/ana.22383 Kim, 2008, PINK1 controls mitochondrial localization of Parkin through direct phosphorylation, Biochemical and Biophysical Research Communications, 377, 975, 10.1016/j.bbrc.2008.10.104 Kimura, 1997, Structure, expression, and chromosomal localization of human GAK, Genomics, 44, 179, 10.1006/geno.1997.4873 Kitada, 2007, Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice, Proceedings of the National Academy of Sciences of the United States of America, 104, 11441, 10.1073/pnas.0702717104 Ko, 2001, p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment, The Journal of Neuroscience, 21, 6758, 10.1523/JNEUROSCI.21-17-06758.2001 Kockeritz, 2006, Glycogen synthase kinase-3 – an overview of an over-achieving protein kinase, Current Drug Targets, 7, 1377, 10.2174/1389450110607011377 Korolchuk, 2002, CK2 and GAK/auxilin2 are major protein kinases in clathrin-coated vesicles, Traffic, 3, 428, 10.1034/j.1600-0854.2002.30606.x Kosik, 2005, Phosphorylated tau and the neurodegenerative foldopathies, Biochimica et Biophysica Acta, 1739, 298, 10.1016/j.bbadis.2004.10.011 Kozikowski, 2006, Highly potent and specific GSK-3beta inhibitors that block tau phosphorylation and decrease alpha-synuclein protein expression in a cellular model of Parkinson's disease, ChemMedChem, 1, 256, 10.1002/cmdc.200500039 Kuan, 2005, Targeting the JNK signaling pathway for stroke and Parkinson's diseases therapy, Current Drug Targets – CNS & Neurological Disorders, 4, 63, 10.2174/1568007053005145 Kumari, 2009, LRRK2 in Parkinson's disease: genetic and clinical studies from patients, The FEBS Journal, 276, 6455, 10.1111/j.1742-4658.2009.07344.x Kwok, 2005, GSK3B polymorphisms alter transcription and splicing in Parkinson's disease, Annals of Neurology, 58, 829, 10.1002/ana.20691 Lee, 2010, Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease, Nature Medicine, 16, 998, 10.1038/nm.2199 Lei, 2011, GSK-3 in Neurodegenerative Diseases, International Journal of Alzheimer's Disease, 2011, 189246, 10.4061/2011/189246 Lev, 2009, DJ-1 protects against dopamine toxicity, Journal of Neural Transmission, 116, 151, 10.1007/s00702-008-0134-4 Li, 2010, Reevaluation of phosphorylation sites in the Parkinson disease-associated leucine-rich repeat kinase 2, The Journal of Biological Chemistry, 285, 29569, 10.1074/jbc.M110.127639 Li, 2007, Leucine-rich repeat kinase 2 (LRRK2)/PARK8 possesses GTPase activity that is altered in familial Parkinson's disease R1441C/G mutants, Journal of Neurochemistry, 103, 238 Li, 2009, Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's disease, Nature Neuroscience, 12, 826, 10.1038/nn.2349 Li, 2005, Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonism, Neurology, 64, 1955, 10.1212/01.WNL.0000164009.36740.4E Lilja, 2004, Cyclin-dependent kinase 5 associated with p39 promotes Munc18-1 phosphorylation and Ca(2+)-dependent exocytosis, The Journal of Biological Chemistry, 279, 29534, 10.1074/jbc.M312711200 Lindgren, 2009, Differential involvement of D1 and D2 dopamine receptors in L-DOPA-induced angiogenic activity in a rat model of Parkinson's disease, Neuropsychopharmacology, 34, 2477, 10.1038/npp.2009.74 Lin, 2009, Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson's-disease-related mutant alpha-synuclein, Neuron, 64, 807, 10.1016/j.neuron.2009.11.006 Liu, 2004, Glycogen synthase kinase 3beta is a negative regulator of growth factor-induced activation of the c-Jun N-terminal kinase, Journal of Biological Chemistry, 279, 51075, 10.1074/jbc.M408607200 Liu, 2011, Inhibitors of LRRK2 kinase attenuate neurodegeneration and Parkinson-like phenotypes in Caenorhabditis elegans and Drosophila Parkinson's disease models, Human Molecular Genetics, 20, 3933, 10.1093/hmg/ddr312 Lopes, 2011, Cdk5: multitasking between physiological and pathological conditions, Progress in Neurobiology, 94, 49, 10.1016/j.pneurobio.2011.03.006 Lucas, 2001, Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice, The EMBO Journal, 20, 27, 10.1093/emboj/20.1.27 MacLeod, 2006, The familial Parkinsonism gene LRRK2 regulates neurite process morphology, Neuron, 52, 587, 10.1016/j.neuron.2006.10.008 Manning, 2002, The protein kinase complement of the human genome, Science, 298, 1912, 10.1126/science.1075762 Matsuda, 2010, Does impairment of the ubiquitin–proteasome system or the autophagy-lysosome pathway predispose individuals to neurodegenerative disorders such as Parkinson's disease?, Journal of Alzheimer's Disease, 19, 1, 10.3233/JAD-2010-1231 Matsui, 1990, Stabilization of clathrin coats by the core of the clathrin-associated protein complex AP-2, Biochemistry, 29, 10791, 10.1021/bi00500a011 Mo, 2010, DJ-1 modulates the p38 mitogen-activated protein kinase pathway through physical interaction with apoptosis signal-regulating kinase 1, Journal of Cellular Biochemistry, 110, 229 Muqit, 2006, Altered cleavage and localization of PINK1 to aggresomes in the presence of proteasomal stress, Journal of Neurochemistry, 98, 156, 10.1111/j.1471-4159.2006.03845.x Naito, 2012, Cyclin G-associated kinase regulates protein phosphatase 2A by phosphorylation of its B’gamma subunit, Cell Cycle, 11, 604, 10.4161/cc.11.3.19114 Nakamura, 1997, p35nck5a and cyclin-dependent kinase 5 colocalize in Lewy bodies of brains with Parkinson's disease, Acta Neuropathologica, 94, 153, 10.1007/s004010050687 Nakaso, 2008, Caffeine activates the PI3K/Akt pathway and prevents apoptotic cell death in a Parkinson's disease model of SH-SY5Y cells, Neuroscience Letters, 432, 146, 10.1016/j.neulet.2007.12.034 Nalls, 2011, Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies, Lancet, 377, 641, 10.1016/S0140-6736(10)62345-8 Newhouse, 2004, Rotenone-induced apoptosis is mediated by p38 and JNK MAP kinases in human dopaminergic SH-SY5Y cells, Toxicological Sciences, 79, 137, 10.1093/toxsci/kfh089 Nolen, 2001, The structure of Sky1p reveals a novel mechanism for constitutive activity, Nature Structural Biology, 8, 176, 10.1038/84178 Ohta, 2011, LRRK2 directly phosphorylates Akt1 as a possible physiological substrate: impairment of the kinase activity by Parkinson's disease-associated mutations, FEBS Letters, 585, 2165, 10.1016/j.febslet.2011.05.044 Owen, 1998, A structural explanation for the recognition of tyrosine-based endocytotic signals, Science, 282, 1327, 10.1126/science.282.5392.1327 Pan, 2010, Small peptide inhibitor of JNKs protects against MPTP-induced nigral dopaminergic injury via inhibiting the JNK-signaling pathway, Laboratory Investigation, 90, 156, 10.1038/labinvest.2009.124 Pan, 2007, K252a prevents nigral dopaminergic cell death induced by 6-hydroxydopamine through inhibition of both mixed-lineage kinase 3/c-Jun NH2-terminal kinase 3 (JNK3) and apoptosis-inducing kinase 1/JNK3 signaling pathways, Molecular Pharmacology, 72, 1607, 10.1124/mol.107.038463 Pan, 2009, Blockade of the translocation and activation of c-Jun N-terminal kinase 3 (JNK3) attenuates dopaminergic neuronal damage in mouse model of Parkinson's disease, Neurochemistry International, 54, 418, 10.1016/j.neuint.2009.01.013 Pan, 2008, The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease, Brain, 131, 1969, 10.1093/brain/awm318 Park, 2006, Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin, Nature, 441, 1157, 10.1038/nature04788 Pavese, 2010, In vivo assessment of brain monoamine systems in parkin gene carriers: a PET study, Experimental Neurology, 222, 120, 10.1016/j.expneurol.2009.12.021 Pavon, 2006, ERK phosphorylation and FosB expression are associated with L-DOPA-induced dyskinesia in hemiparkinsonian mice, Biological Psychiatry, 59, 64, 10.1016/j.biopsych.2005.05.044 Pearson, 2001, Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions, Endocrine Reviews, 22, 153 Pei, 2006, Neuroprotection against ischaemic brain injury by a GluR6-9c peptide containing the TAT protein transduction sequence, Brain, 129, 465, 10.1093/brain/awh700 Peng, 2004, The herbicide paraquat induces dopaminergic nigral apoptosis through sustained activation of the JNK pathway, The Journal of Biological Chemistry, 279, 32626, 10.1074/jbc.M404596200 Piccoli, 2011, LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool, The Journal of Neuroscience, 31, 2225, 10.1523/JNEUROSCI.3730-10.2011 Plowey, 2008, Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells, Journal of Neurochemistry, 105, 1048, 10.1111/j.1471-4159.2008.05217.x Plun-Favreau, 2007, The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1, Nature Cell Biology, 9, 1243, 10.1038/ncb1644 Poole, 2010, The mitochondrial fusion-promoting factor mitofusin is a substrate of the PINK1/parkin pathway, PLoS One, 5, e10054, 10.1371/journal.pone.0010054 Pridgeon, 2007, PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1, PLoS Biology, 5, e172, 10.1371/journal.pbio.0050172 Qin, 2011, Protection by tetrahydroxystilbene glucoside against neurotoxicity induced by MPP+: the involvement of PI3K/Akt pathway activation, Toxicology Letters, 202, 1, 10.1016/j.toxlet.2011.01.001 Ramsden, 2011, Chemoproteomics-based design of potent LRRK2-selective lead compounds that attenuate Parkinson's disease-related toxicity in human neurons, ACS Chemical Biology, 6, 1021, 10.1021/cb2002413 Ran, 2011, Genetic studies of the protein kinase AKT1 in Parkinson's disease, Neuroscience Letters, 501, 41, 10.1016/j.neulet.2011.06.038 Ray, 2006, Cyclin G-associated kinase: a novel androgen receptor-interacting transcriptional coactivator that is overexpressed in hormone refractory prostate cancer, International Journal of Cancer, 118, 1108, 10.1002/ijc.21469 Rhodes, 2011, Replication of GWAS associations for GAK and MAPT in Parkinson's disease, Annals of Human Genetics, 75, 195 Rosales, 2006, Extraneuronal roles of cyclin-dependent kinase 5, Bioessays, 28, 1023, 10.1002/bies.20473 Rosales, 2000, Cdk5/p25(nck5a) interaction with synaptic proteins in bovine brain, Journal of Cellular Biochemistry, 78, 151, 10.1002/(SICI)1097-4644(20000701)78:1<151::AID-JCB14>3.0.CO;2-L Rubinfeld, 1996, Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly, Science, 272, 1023, 10.1126/science.272.5264.1023 Salminen, 2011, AMP-activated protein kinase: a potential player in Alzheimer's disease, Journal of Neurochemistry, 118, 460, 10.1111/j.1471-4159.2011.07331.x Sanchez, 2000, GSK3beta-mediated phosphorylation of the microtubule-associated protein 2C (MAP2C) prevents microtubule bundling, European Journal of Cell Biology, 79, 252, 10.1078/S0171-9335(04)70028-X Sanchez-Mora, 2012, PINK1 overexpression protects against C2-ceramide-induced CAD cell death through the PI3K/AKT pathway, Journal of Molecular Neuroscience, 47, 582, 10.1007/s12031-011-9687-z Santini, 2009, l-DOPA activates ERK signaling and phosphorylates histone H3 in the striatonigral medium spiny neurons of hemiparkinsonian mice, Journal of Neurochemistry, 108, 621, 10.1111/j.1471-4159.2008.05831.x Santini, 2010, Distinct changes in cAMP and extracellular signal-regulated protein kinase signalling in l-DOPA-induced dyskinesia, PLoS One, 5, e12322, 10.1371/journal.pone.0012322 Santini, 2007, Critical involvement of cAMP/DARPP-32 and extracellular signal-regulated protein kinase signaling in l-DOPA-induced dyskinesia, The Journal of Neuroscience, 27, 6995, 10.1523/JNEUROSCI.0852-07.2007 Sato, 2009, GAK, a regulator of clathrin-mediated membrane trafficking, localizes not only in the cytoplasm but also in the nucleus, Genes Cells, 14, 627, 10.1111/j.1365-2443.2009.01296.x Schapira, 2009, Etiology and pathogenesis of Parkinson disease, Neurologic Clinics, 27, 583, 10.1016/j.ncl.2009.04.004 Schubert, 2010, beta2-Syntrophin is a Cdk5 substrate that restrains the motility of insulin secretory granules, PLoS One, 5, e12929, 10.1371/journal.pone.0012929 Shaw, 1998, Isolation and chromosomal mapping of human glycogen synthase kinase-3 alpha and -3 beta encoding genes, Genome, 41, 720 Shimizu, 2009, GAK, a regulator of clathrin-mediated membrane traffic, also controls centrosome integrity and chromosome congression, Journal of Cell Science, 122, 3145, 10.1242/jcs.052795 Shimomura, 2011, Evidence for amylase release by cyclin-dependent kinase 5 in the rat parotid, Archives of Biochemistry and Biophysics, 507, 310, 10.1016/j.abb.2010.12.025 Silva, 2005, Mixed lineage kinase-c-jun N-terminal kinase signaling pathway: a new therapeutic target in Parkinson's disease, Movement Disorders, 20, 653, 10.1002/mds.20390 Silvestri, 2005, Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism, Human Molecular Genetics, 14, 3477, 10.1093/hmg/ddi377 Sim, 2006, C-terminal truncation and Parkinson's disease-associated mutations down-regulate the protein serine/threonine kinase activity of PTEN-induced kinase-1, Human Molecular Genetics, 15, 3251, 10.1093/hmg/ddl398 Sitaram, 2009, The PTEN regulator DJ-1 is associated with hTERT expression in clear cell renal cell carcinoma, International Journal of Cancer, 125, 783, 10.1002/ijc.24335 Smith, 2003, Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson's disease, Proceedings of the National Academy of Sciences of the United States of America, 100, 13650, 10.1073/pnas.2232515100 Smith, 2006, Calpain-regulated p35/cdk5 plays a central role in dopaminergic neuron death through modulation of the transcription factor myocyte enhancer factor 2, The Journal of Neuroscience, 26, 440, 10.1523/JNEUROSCI.2875-05.2006 Smith, 2006, Kinase activity of mutant LRRK2 mediates neuronal toxicity, Nature Neuroscience, 9, 1231, 10.1038/nn1776 Song, 2005, The activation of Akt/PKB signaling pathway and cell survival, Journal of Cellular and Molecular Medicine, 9, 59, 10.1111/j.1582-4934.2005.tb00337.x Songin, 2011, Glycogen synthase kinase 3beta and its phosphorylated form (Y216) in the paraquat-induced model of parkinsonism, Neurotoxicity Research, 19, 162, 10.1007/s12640-010-9153-7 Soutar, 2010, Evidence that glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain, Journal of Neurochemistry, 115, 974, 10.1111/j.1471-4159.2010.06988.x Sundal, 2012, Autosomal dominant Parkinson's disease, Parkinsonism & Related Disorders, 18, S7, 10.1016/S1353-8020(11)70005-0 Susa, 2010, Cyclin G-associated kinase is necessary for osteosarcoma cell proliferation and receptor trafficking, Molecular Cancer Therapeutics, 9, 3342, 10.1158/1535-7163.MCT-10-0637 Tanenbaum, 2010, Cyclin G-associated kinase promotes microtubule outgrowth from chromosomes during spindle assembly, Chromosoma, 119, 415, 10.1007/s00412-010-0267-8 Tian, 2010, Potential roles of Cdk5/p35 and tau protein in hippocampal mossy fiber sprouting in the PTZ kindling model, Clinical Laboratory, 56, 127 Timmons, 2009, Akt signal transduction dysfunction in Parkinson's disease, Neuroscience Letters, 467, 30, 10.1016/j.neulet.2009.09.055 Tomiyama, 2009, Mutation analysis for DJ-1 in sporadic and familial parkinsonism: screening strategy in parkinsonism, Neuroscience Letters, 455, 159, 10.1016/j.neulet.2009.03.033 Tomizawa, 2002, Cdk5/p35 regulates neurotransmitter release through phosphorylation and downregulation of P/Q-type voltage-dependent calcium channel activity, The Journal of Neuroscience, 22, 2590, 10.1523/JNEUROSCI.22-07-02590.2002 Tong, 2009, alpha-Synuclein and LRRK2: partners in crime, Neuron, 64, 771, 10.1016/j.neuron.2009.12.017 Valente, 2004, Hereditary early-onset Parkinson's disease caused by mutations in PINK1, Science, 304, 1158, 10.1126/science.1096284 Valente, 2001, Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36, American Journal of Human Genetics, 68, 895, 10.1086/319522 Vasudevan, 2010, AKT signaling in physiology and disease, Current Topics in Microbiology and Immunology, 347, 105 Waak, 2009, Regulation of astrocyte inflammatory responses by the Parkinson's disease-associated gene DJ-1, The FASEB Journal, 23, 2478, 10.1096/fj.08-125153 Waldmeier, 2006, Recent clinical failures in Parkinson's disease with apoptosis inhibitors underline the need for a paradigm shift in drug discovery for neurodegenerative diseases, Biochemical Pharmacology, 72, 1197, 10.1016/j.bcp.2006.06.031 Walker, 2005, Targeting Ras and Rho GTPases as opportunities for cancer therapeutics, Current Opinion in Genetics & Development, 15, 62, 10.1016/j.gde.2004.11.001 Wang, 2005, PACAP protects neuronal differentiated PC12 cells against the neurotoxicity induced by a mitochondrial complex I inhibitor, rotenone, FEBS Letters, 579, 4005, 10.1016/j.febslet.2005.06.013 Wang, 2010, Insulin-like growth factor 1 protects human neuroblastoma cells SH-EP1 against MPP+-induced apoptosis by AKT/GSK-3beta/JNK signaling, Apoptosis, 15, 1470, 10.1007/s10495-010-0547-z Wang, 2008, Mixed lineage kinase inhibitor CEP-1347 fails to delay disability in early Parkinson disease, Neurology, 71, 462, 10.1212/01.wnl.0000324506.93877.5e Wang, 2007, Inhibition of glycogen synthase kinase-3beta protects dopaminergic neurons from MPTP toxicity, Neuropharmacology, 52, 1678, 10.1016/j.neuropharm.2007.03.017 Wang, 2009, JNK inhibitor protects dopaminergic neurons by reducing COX-2 expression in the MPTP mouse model of subacute Parkinson's disease, Journal of the neurological sciences, 285, 172, 10.1016/j.jns.2009.06.034 Wang, 2011, DJ-1 modulates the expression of Cu/Zn-superoxide dismutase-1 through the Erk1/2-Elk1 pathway in neuroprotection, Annals of Neurology, 70, 591, 10.1002/ana.22514 Wei, 2005, Cdk5-dependent regulation of glucose-stimulated insulin secretion, Nature Medicine, 11, 1104, 10.1038/nm1299 Weng, 2007, PINK1 mutation in Taiwanese early-onset parkinsonism: clinical, genetic, and dopamine transporter studies, Journal of Neurology, 254, 1347, 10.1007/s00415-007-0534-7 Wilms, 2003, Activation of microglia by human neuromelanin is NF-kappaB dependent and involves p38 mitogen-activated protein kinase: implications for Parkinson's disease, The FASEB Journal, 17, 500, 10.1096/fj.02-0314fje Wong, 2011, Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson's disease, Nature Cell Biology, 13, 568, 10.1038/ncb2217 Woodgett, 1990, Molecular cloning and expression of glycogen synthase kinase-3/factor A, The EMBO Journal, 9, 2431, 10.1002/j.1460-2075.1990.tb07419.x Xiong, 2010, GTPase activity plays a key role in the pathobiology of LRRK2, PLoS Genetics, 6, e1000902, 10.1371/journal.pgen.1000902 Xiromerisiou, 2008, Association between AKT1 gene and Parkinson's disease: a protective haplotype, Neuroscience Letters, 436, 232, 10.1016/j.neulet.2008.03.026 Yang, 2005, Inactivation of Drosophila DJ-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase/Akt signaling, Proceedings of the National Academy of Sciences of the United States of America, 102, 13670, 10.1073/pnas.0504610102 Yasuda, 2011, p38 MAP kinase inhibitors as potential therapeutic drugs for neural diseases, Central Nervous System Agents in Medicinal Chemistry, 11, 45, 10.2174/187152411794961040 Yong, 2009, The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer, Expert Opinion on Investigational Drugs, 18, 1893, 10.1517/13543780903321490 Yun, 2011, Identification of chemicals to inhibit the kinase activity of leucine-rich repeat kinase 2 (LRRK2), a Parkinson's disease-associated protein, Bioorganic & Medicinal Chemistry Letters, 21, 2953, 10.1016/j.bmcl.2011.03.061 Yun, 2008, Loss-of-function analysis suggests that Omi/HtrA2 is not an essential component of the PINK1/PARKIN pathway in vivo, The Journal of Neuroscience, 28, 14500, 10.1523/JNEUROSCI.5141-08.2008 Zawada, 2001, Inhibitors of p38 MAP kinase increase the survival of transplanted dopamine neurons, Brain Research, 891, 185, 10.1016/S0006-8993(00)02965-6 Zhang, 2004, The serine/threonine kinase cyclin G-associated kinase regulates epidermal growth factor receptor signaling, Proceedings of the National Academy of Sciences of the United States of America, 101, 10296, 10.1073/pnas.0403175101 Zimprich, 2011, Genetics of Parkinson's disease and essential tremor, Current Opinion in Neurology, 24, 318, 10.1097/WCO.0b013e3283484b87