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

Progress in Neurobiology

Volumn 98, Issue 2, 2012, Pages 207-221

  Wang, Gang ^a   Pan, Jing ^a   Chen, Sheng Di ^a,b  

^a SHANGHAI SECOND MEDICAL UNIVERSITY   (China)

^b SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

Author keywords

Gene mutation; Kinase; Parkinson's disease; Pathogenesis; Phosphorylation signaling pathway; Therapeutic target

Indexed keywords

CYCLIN DEPENDENT KINASE 5; CYCLIN G; CYCLIN G ASSOCIATED KINASE; GLYCOGEN SYNTHASE KINASE 3BETA; LEUCINE RICH REPEAT KINASE 2; LEVODOPA; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE P38; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE INDUCED KINASE 1; PHOSPHOTRANSFERASE; PROTEIN KINASE B; STRESS ACTIVATED PROTEIN KINASE; TAU PROTEIN; UNCLASSIFIED DRUG;

ENZYME ACTIVITY; GENE PRODUCT; GENETIC ASSOCIATION; NEUROMODULATION; NONHUMAN; PARKINSON DISEASE; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; BRAIN; HUMANS; PARKINSON DISEASE; PHOSPHOTRANSFERASES; SIGNAL TRANSDUCTION;

EID: 84863107192     PISSN: 03010082     EISSN: 18735118     Source Type: Journal    
DOI: 10.1016/j.pneurobio.2012.06.003     Document Type: Review

References (212)

1. Abdalla-Carvalho C.B., Santos-Reboucas C.B., Guimaraes B.C., Campos M., Pereira J.S., de Rosso A.L., Nicaretta D.H., Marinho e Silva M., dos Santos M.J., Pimentel M.M. Genetic analysis of LRRK2 functional domains in Brazilian patients with Parkinson's disease. European Journal of Neurology 2010, 17:1479-1481.
2. Abeliovich A. Parkinson's disease: pro-survival effects of PINK1. Nature 2007, 448:759-760.
3. Abou-Sleiman P.M., Muqit M.M., McDonald N.Q., Yang Y.X., Gandhi S., Healy D.G., Harvey K., Harvey R.J., Deas E., Bhatia K., Quinn N., Lees A., Latchman D.S., Wood N.W. A heterozygous effect for PINK1 mutations in Parkinson's disease?. Annals of Neurology 2006, 60:414-419.
4. Akundi R.S., Huang Z., Eason J., Pandya J.D., Zhi L., Cass W.A., Sullivan P.G., Bueler H. Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice. PLoS One 2011, 6:e16038.
5. Akundi R.S., Zhi L., Bueler H. PINK1 enhances insulin-like growth factor-1-dependent Akt signaling and protection against apoptosis. Neurobiology of Disease 2012, 45:469-478.
6. Aleyasin H., Rousseaux M.W., Marcogliese P.C., Hewitt S.J., Irrcher I., Joselin A.P., Parsanejad M., Kim R.H., Rizzu P., Callaghan S.M., Slack R.S., Mak T.W., Park D.S. 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 2010, 107:3186-3191.
7. Alnemri E.S. HtrA2 and Parkinson's disease: think PINK?. Nature Cell Biology 2007, 9:1227-1229.
8. Amin N.D., Albers W., Pant H.C. Cyclin-dependent kinase 5 (cdk5) activation requires interaction with three domains of p35. Journal of Neuroscience Research 2002, 67:354-362.
9. Benamer H.T., de Silva R. LRRK2 G2019S in the North African population: a review. European Neurology 2010, 63:321-325.
10. Berwick D.C., Harvey K. LRRK2 signaling pathways: the key to unlocking neurodegeneration?. Trends in Cell Biology 2011, 21:257-265.
11. Bishop M.W., Chakraborty S., Matthews G.A., Dougalis A., Wood N.W., Festenstein R., Ungless M.A. Hyperexcitable substantia nigra dopamine neurons in PINK1- and HtrA2/Omi-deficient mice. Journal of Neurophysiology 2010, 104:3009-3020.
12. Biskup S., Moore D.J., Celsi F., Higashi S., West A.B., Andrabi S.A., Kurkinen K., Yu S.W., Savitt J.M., Waldvogel H.J., Faull R.L., Emson P.C., Torp R., Ottersen O.P., Dawson T.M., Dawson V.L. Localization of LRRK2 to membranous and vesicular structures in mammalian brain. Annals of Neurology 2006, 60:557-569.
13. Bonifati V. Shaking the genome: new studies reveal genetic risk for Parkinson's disease. The Lancet Neurology 2010, 9:136-138.
14. Bonifati V. Autosomal recessive parkinsonism. Parkinsonism & Related Disorders 2012, 18(Suppl 1):S4-S6.
15. Borsello T., Forloni G. JNK signalling: a possible target to prevent neurodegeneration. Current Pharmaceutical Design 2007, 13:1875-1886.
16. Braak H., Ghebremedhin E., Rub U., Bratzke H., Del Tredici K. Stages in the development of Parkinson's disease-related pathology. Cell and Tissue Research 2004, 318:121-134.
17. Braithwaite S.P., Stock J.B., Mouradian M.M. alpha-Synuclein phosphorylation as a therapeutic target in Parkinson's disease. Reviews in the Neurosciences 2012, 23:191-198.
18. Braithwaite S.P., Voronkov M., Stock J.B., Mouradian M.M. Targeting phosphatases as the next generation of disease modifying therapeutics for Parkinson's disease. Neurochemistry International 2012.
19. Brambilla R. Targeting Ras/ERK signaling in the striatum: will it help?. Molecular Psychiatry 2003, 8:366-368.
20. Brion J.P., Couck A.M. Cortical and brainstem-type Lewy bodies are immunoreactive for the cyclin-dependent kinase 5. American Journal of Pathology 1995, 147:1465-1476.
21. Cali T., Ottolini D., Brini M. Mitochondria, calcium, and endoplasmic reticulum stress in Parkinson's disease. Biofactors 2011, 37:228-240. 10.1002/biof.159.
22. Camins A., Verdaguer E., Folch J., Canudas A.M., Pallas M. The role of CDK5/P25 formation/inhibition in neurodegeneration. Drug News & Perspectives 2006, 19:453-460.
23. Carballo-Carbajal I., Weber-Endress S., Rovelli G., Chan D., Wolozin B., Klein C.L., Patenge N., Gasser T., Kahle P.J. Leucine-rich repeat kinase 2 induces alpha-synuclein expression via the extracellular signal-regulated kinase pathway. Cellular Signalling 2010, 22:821-827.
24. Cassarino D.S., Halvorsen E.M., Swerdlow R.H., Abramova N.N., Parker W.D., Sturgill T.W., Bennett J.P. Interaction among mitochondria, mitogen-activated protein kinases, and nuclear factor-kappaB in cellular models of Parkinson's disease. Journal of Neurochemistry 2000, 74:1384-1392.
25. Chan D., Citro A., Cordy J.M., Shen G.C., Wolozin B. Rac1 protein rescues neurite retraction caused by G2019S leucine-rich repeat kinase 2 (LRRK2). The Journal of Biological Chemistry 2011, 286:16140-16149.
26. Cheng B., Maffi S.K., Martinez A.A., Acosta Y.P., Morales L.D., Roberts J.L. Insulin-like growth factor-I mediates neuroprotection in proteasome inhibition-induced cytotoxicity in SH-SY5Y cells. Molecular and Cellular Neurosciences 2011, 47:181-190.
27. Cheng T.S., Hsiao Y.L., Lin C.C., Yu C.T., Hsu C.M., Chang M.S., Lee C.I., Huang C.Y., Howng S.L., Hong Y.R. Glycogen synthase kinase 3beta interacts with and phosphorylates the spindle-associated protein astrin. The Journal of Biological Chemistry 2008, 283:2454-2464.
28. Chien W.L., Lee T.R., Hung S.Y., Kang K.H., Lee M.J., Fu W.M. Impairment of oxidative stress-induced heme oxygenase-1 expression by the defect of Parkinson-related gene of PINK1. Journal of Neurochemistry 2011, 117:643-653. 10.1111/j. 1471-4159.2011.07229.x.
29. Choi W.S., Eom D.S., Han B.S., Kim W.K., Han B.H., Choi E.J., Oh T.H., Markelonis G.J., Cho J.W., Oh Y.J. 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 2004, 279:20451-20460.
30. Cohen P., Frame S. The renaissance of GSK3. Nature Reviews. Molecular Cell Biology 2001, 2:769-776.
31. Cole A.R., Causeret F., Yadirgi G., Hastie C.J., McLauchlan H., McManus E.J., Hernandez F., Eickholt B.J., Nikolic M., Sutherland C. Distinct priming kinases contribute to differential regulation of collapsin response mediator proteins by glycogen synthase kinase-3 in vivo. The Journal of Biological Chemistry 2006, 281:16591-16598.
32. Conner S.D., Schroter T., Schmid S.L. AAK1-mediated micro2 phosphorylation is stimulated by assembled clathrin. Traffic 2003, 4:885-890.
33. Cook C., Petrucelli L. A critical evaluation of the ubiquitin-proteasome system in Parkinson's disease. Biochimica et Biophysica Acta 2009, 1792:664-675.
34. Cookson M.R. The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease. Nature Reviews Neuroscience 2010, 11:791-797.
35. Cookson M.R., Dauer W., Dawson T., Fon E.A., Guo M., Shen J. The roles of kinases in familial Parkinson's disease. The Journal of Neuroscience 2007, 27:11865-11868.
36. Cornejo Castro E.M., Waak J., Weber S.S., Fiesel F.C., Oberhettinger P., Schutz M., Autenrieth I.B., Springer W., Kahle P.J. Parkinson's disease-associated DJ-1 modulates innate immunity signaling in Caenorhabditis elegans. Journal of Neural Transmission 2010, 117:599-604.
37. Cuny G.D. Kinase inhibitors as potential therapeutics for acute and chronic neurodegenerative conditions. Current Pharmaceutical Design 2009, 15:3919-3939.
38. Dagda R.K., Zhu J., Chu C.T. Mitochondrial kinases in Parkinson's disease: converging insights from neurotoxin and genetic models. Mitochondrion 2009, 9:289-298.
39. Das Evcimen N., King G.L. The role of protein kinase C activation and the vascular complications of diabetes. Pharmacological Research 2007, 55:498-510.
40. Das G., Misra A.K., Das S.K., Ray K., Ray J. Role of tau kinases (CDK5R1 and GSK3B) in Parkinson's disease: a study from India. Neurobiology of Aging 2012, 33:1485.e9-1485.e15.
41. Deas E., Wood N.W., Plun-Favreau H. Mitophagy and Parkinson's disease: the PINK1-parkin link. Biochimica et Biophysica Acta 2011, 1813:623-633.
42. Demetrick D.J., Zhang H., Beach D.H. Chromosomal mapping of human CDK2, CDK4, and CDK5 cell cycle kinase genes. Cytogenetics and Cell Genetics 1994, 66:72-74.
43. Deng X., Dzamko N., Prescott A., Davies P., Liu Q., Yang Q., Lee J.D., Patricelli M.P., Nomanbhoy T.K., Alessi D.R., Gray N.S. Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2. Nature Chemical Biology 2011, 7:203-205.
44. Duka T., Duka V., Joyce J.N., Sidhu A. Alpha-Synuclein contributes to GSK-3beta-catalyzed Tau phosphorylation in Parkinson's disease models. The FASEB Journal 2009, 23:2820-2830.
45. Dumitriu A., Pacheco C.D., Wilk J.B., Strathearn K.E., Latourelle J.C., Goldwurm S., Pezzoli G., Rochet J.C., Lindquist S., Myers R.H. Cyclin-G-associated kinase modifies alpha-synuclein expression levels and toxicity in Parkinson's disease: results from the GenePD study. Human Molecular Genetics 2011, 20:1478-1487.
46. Eggers C., Schmidt A., Hagenah J., Bruggemann N., Klein J.C., Tadic V., Kertelge L., Kasten M., Binkofski F., Siebner H., Neumaier B., Fink G.R., Hilker R., Klein C. Progression of subtle motor signs in PINK1 mutation carriers with mild dopaminergic deficit. Neurology 2010, 74:1798-1805.
47. Elstner M., Morris C.M., Heim K., Bender A., Mehta D., Jaros E., Klopstock T., Meitinger T., Turnbull D.M., Prokisch H. Expression analysis of dopaminergic neurons in Parkinson's disease and aging links transcriptional dysregulation of energy metabolism to cell death. Acta Neuropathologica 2011, 122:75-86.
48. Farghaian H., Turnley A.M., Sutherland C., Cole A.R. Bioinformatic prediction and confirmation of beta-adducin as a novel substrate of glycogen synthase kinase 3. The Journal of Biological Chemistry 2011, 286:25274-25283.
49. Faris M., Latinis K.M., Kempiak S.J., Koretzky G.A., Nel A. 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 1998, 18:5414-5424.
50. Fayard E., Xue G., Parcellier A., Bozulic L., Hemmings B.A. Protein kinase B (PKB/Akt), a key mediator of the PI3K signaling pathway. Current Topics in Microbiology and Immunology 2010, 346:31-56.
51. Fischer A., Sananbenesi F., Spiess J., Radulovic J. Cdk5 in the adult non-demented brain. Current Drug Targets - CNS & Neurological Disorders 2003, 2:375-381.
52. Fritz G., Kaina B. Rho GTPases: promising cellular targets for novel anticancer drugs. Current Cancer Drug Targets 2006, 6:1-14.
53. Fu Q.S., Song A.X., Li S.X., Hu H.Y. The small GTPase activity of the ROC domain from LRRK2, a Parkinson's disease related protein. Protein and Peptide Letters 2009, 16:1442-1446.
54. Fujioka S., Wszolek Z.K. Update on Genetics of Parkinsonism. Neurodegenerative Diseases 2012, 10:257-260.
55. Funayama M., Hasegawa K., Kowa H., Saito M., Tsuji S., Obata F. A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1. Annals of Neurology 2002, 51:296-301.
56. Gallo K.A., Johnson G.L. Mixed-lineage kinase control of JNK and p38 MAPK pathways. Nature Reviews. Molecular Cell Biology 2002, 3:663-672.
57. Gandhi S., Muqit M.M., Stanyer L., Healy D.G., Abou-Sleiman P.M., Hargreaves I., Heales S., Ganguly M., Parsons L., Lees A.J., Latchman D.S., Holton J.L., Wood N.W., Revesz T. PINK1 protein in normal human brain and Parkinson's disease. Brain 2006, 129:1720-1731.
58. Ghazavi F., Fazlali Z., Banihosseini S.S., Hosseini S.R., Kazemi M.H., Shojaee S., Parsa K., Sadeghi H., Sina F., Rohani M., Shahidi G.A., Ghaemi N., Ronaghi M., Elahi E. PRKN, DJ-1, and PINK1 screening identifies novel splice site mutation in PRKN and two novel DJ-1 mutations. Movement Disorders 2011, 26:80-89. 10.1002/mds.23417.
59. Ghigo A., Damilano F., Braccini L., Hirsch E. PI3K inhibition in inflammation: toward tailored therapies for specific diseases. Bioessays 2010, 32:185-196.
60. Gloeckner C.J., Boldt K., von Zweydorf F., Helm S., Wiesent L., Sarioglu H., Ueffing M. 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 2010, 9:1738-1745.
61. Gloeckner C.J., Schumacher A., Boldt K., Ueffing M. The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro. Journal of Neurochemistry 2009, 109:959-968.
62. Goold R.G., Gordon-Weeks P.R. Microtubule-associated protein 1B phosphorylation by glycogen synthase kinase 3beta is induced during PC12 cell differentiation. Journal of Cell Science 2001, 114:4273-4284.
63. Greenamyre J.T., Hastings T.G. Biomedicine. Parkinson's - divergent causes, convergent mechanisms. Science 2004, 304:1120-1122.
64. Greener T., Zhao X., Nojima H., Eisenberg E., Greene L.E. Role of cyclin G-associated kinase in uncoating clathrin-coated vesicles from non-neuronal cells. The Journal of Biological Chemistry 2000, 275:1365-1370.
65. Greggio E., Jain S., Kingsbury A., Bandopadhyay R., Lewis P., Kaganovich A., van der Brug M.P., Beilina A., Blackinton J., Thomas K.J., Ahmad R., Miller D.W., Kesavapany S., Singleton A., Lees A., Harvey R.J., Harvey K., Cookson M.R. Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiology of Disease 2006, 23:329-341.
66. Greggio E., Singleton A. Kinase signaling pathways as potential targets in the treatment of Parkinson's disease. Expert Review of Proteomics 2007, 4:783-792.
67. Guan Q., Liu X., He Y., Jin L., Zhao L. Effect of cdk5 antagonist on l-dopa-induced dyskinesias in a rat model of Parkinson's disease. The International Journal of Neuroscience 2010, 120:421-427.
68. Gu L., Cui T., Fan C., Zhao H., Zhao C., Lu L., Yang H. Involvement of ERK1/2 signaling pathway in DJ-1-induced neuroprotection against oxidative stress. Biochemical and Biophysical Research Communications 2009, 383:469-474.
69. Gu M., Schuske K., Watanabe S., Liu Q., Baum P., Garriga G., Jorgensen E.M. Mu2 adaptin facilitates but is not essential for synaptic vesicle recycling in Caenorhabditis elegans. The Journal of Cell Biology 2008, 183:881-892.
70. Harper S.J., Wilkie N. MAPKs: new targets for neurodegeneration. Expert Opinion on Therapeutic Targets 2003, 7:187-200.
71. Hernandez F., Nido J.D., Avila J., Villanueva N. GSK3 inhibitors and disease. Mini Reviews in Medicinal Chemistry 2009, 9:1024-1029.
72. Higashi S., Iseki E., Minegishi M., Togo T., Kabuta T., Wada K. GIGYF2 is present in endosomal compartments in the mammalian brains and enhances IGF-1-induced ERK1/2 activation. Journal of Neurochemistry 2010, 115:423-437. 10.1111/j. 1471-4159.2010.06930.x.
73. Honing S., Ricotta D., Krauss M., Spate K., Spolaore B., Motley A., Robinson M., Robinson C., Haucke V., Owen D.J. Phosphatidylinositol-(4,5)-bisphosphate regulates sorting signal recognition by the clathrin-associated adaptor complex AP2. Molecular Cell 2005, 18:519-531.
74. Ho W.L., Ho W.M., Liu H.F., So H.F., Tse H.M., Chan K.H., Ramsden Band, Ho S.L. Mitochondrial neuronal uncoupling proteins: a target for potential disease-modification in Parkinson's disease. Translational Neurodegeneration 2012, 1:3.
75. Hsu C.H., Chan D., Greggio E., Saha S., Guillily M.D., Ferree A., Raghavan K., Shen G.C., Segal L., Ryu H., Cookson M.R., Wolozin B. MKK6 binds and regulates expression of Parkinson's disease-related protein LRRK2. Journal of Neurochemistry 2010, 112:1593-1604.
76. Hsu C.H., Chan D., Wolozin B. LRRK2 and the stress response: interaction with MKKs and JNK-interacting proteins. Neurodegenerative Diseases 2010, 7:68-75.
77. Hwang S., Kim D., Choi G., An S.W., Hong Y.K., Suh Y.S., Lee M.J., Cho K.S. Parkin suppresses c-Jun N-terminal kinase-induced cell death via transcriptional regulation in Drosophila. Molecular Cell 2010, 29:575-580.
78. Infante J., Garcia-Gorostiaga I., Sanchez-Juan P., Sierra M., Martin-Gurpegui J.L., Terrazas J., Mateo I., Rodriguez-Rodriguez E., Berciano J., Combarros O. Synergistic effect of two oxidative stress-related genes (heme oxygenase-1 and GSK3beta) on the risk of Parkinson's disease. European Journal of Neurology 2010, 17:760-762.
79. Imai Y., Gehrke S., Wang H.Q., Takahashi R., Hasegawa K., Oota E., Lu B. Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila. The EMBO Journal 2008, 27:2432-2443.
80. Jaleel M., Nichols R.J., Deak M., Campbell D.G., Gillardon F., Knebel A., Alessi D.R. LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson's disease mutants affect kinase activity. The Biochemical Journal 2007, 405:307-317.
81. Jankowski M. [The role of JNK pathway in familial Parkinson's disease]. Postepy Biochemii 2007, 53:297-303.
82. Jope R.S., Johnson G.V. The glamour and gloom of glycogen synthase kinase-3. Trends in Biochemical Sciences 2004, 29:95-102.
83. Kaidanovich-Beilin O., Woodgett J.R. GSK-3: functional insights from cell biology and animal models. Frontiers in Molecular Neuroscience 2011, 4:40.
84. Kalinderi K., Fidani L., Katsarou Z., Clarimon J., Bostantjopoulou S., Kotsis A. GSK3beta polymorphisms, MAPT H1 haplotype and Parkinson's disease in a Greek cohort. Neurobiology of Aging 2011, 32(546):e541-e545.
85. Kamikawaji S., Ito G., Iwatsubo T. Identification of the autophosphorylation sites of LRRK2. Biochemistry 2009, 48:10963-10975.
86. Kanaoka Y., Kimura S.H., Okazaki I., Ikeda M., Nojima H. GAK: a cyclin G associated kinase contains a tensin/auxilin-like domain. FEBS Letters 1997, 402:73-80.
87. Karunakaran S., Ravindranath V. 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 2009, 109:1791-1799.
88. Karunakaran S., Saeed U., Mishra M., Valli R.K., Joshi S.D., Meka D.P., Seth P., Ravindranath V. 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 2008, 28:12500-12509.
89. Kawakami F., Suzuki M., Shimada N., Kagiya G., Ohta E., Tamura K., Maruyama H., Ichikawa T. Stimulatory effect of alpha-synuclein on the tau-phosphorylation by GSK-3beta. The FEBS Journal 2011, 278:4895-4904.
90. Khan N.L., Jain S., Lynch J.M., Pavese N., Abou-Sleiman P., Holton J.L., Healy D.G., Gilks W.P., Sweeney M.G., Ganguly M., Gibbons V., Gandhi S., Vaughan J., Eunson L.H., Katzenschlager R., Gayton J., Lennox G., Revesz T., Nicholl D., Bhatia K.P., Quinn N., Brooks D., Lees A.J., Davis M.B., Piccini P., Singleton A.B., Wood N.W. Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data. Brain 2005, 128:2786-2796.
91. Kim A.H., Khursigara G., Sun X., Franke T.F., Chao M.V. Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1. Molecular and Cellular Biology 2001, 21:893-901.
92. Kim A.H., Yano H., Cho H., Meyer D., Monks B., Margolis B., Birnbaum M.J., Chao M.V. Akt1 regulates a JNK scaffold during excitotoxic apoptosis. Neuron 2002, 35:697-709.
93. Kim S.R., Chen X., Oo T.F., Kareva T., Yarygina O., Wang C., During M., Kholodilov N., Burke R.E. Dopaminergic pathway reconstruction by Akt/Rheb-induced axon regeneration. Annals of Neurology 2011, 70:110-120. 10.1002/ana.22383.
94. Kim Y., Park J., Kim S., Song S., Kwon S.K., Lee S.H., Kitada T., Kim J.M., Chung J. PINK1 controls mitochondrial localization of Parkin through direct phosphorylation. Biochemical and Biophysical Research Communications 2008, 377:975-980.
95. Kimura S.H., Tsuruga H., Yabuta N., Endo Y., Nojima H. Structure, expression, and chromosomal localization of human GAK. Genomics 1997, 44:179-187.
96. Kitada T., Pisani A., Porter D.R., Yamaguchi H., Tscherter A., Martella G., Bonsi P., Zhang C., Pothos E.N., Shen J. 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 2007, 104:11441-11446.
97. Ko J., Humbert S., Bronson R.T., Takahashi S., Kulkarni A.B., Li E., Tsai L.H. p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment. The Journal of Neuroscience 2001, 21:6758-6771.
98. Kockeritz L., Doble B., Patel S., Woodgett J.R. Glycogen synthase kinase-3 - an overview of an over-achieving protein kinase. Current Drug Targets 2006, 7:1377-1388.
99. Korolchuk V.I., Banting G. CK2 and GAK/auxilin2 are major protein kinases in clathrin-coated vesicles. Traffic 2002, 3:428-439.
100. Kosik K.S., Shimura H. Phosphorylated tau and the neurodegenerative foldopathies. Biochimica et Biophysica Acta 2005, 1739:298-310.
101. Kozikowski A.P., Gaisina I.N., Petukhov P.A., Sridhar J., King L.T., Blond S.Y., Duka T., Rusnak M., Sidhu A. 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 2006, 1:256-266.
102. Kuan C.Y., Burke R.E. Targeting the JNK signaling pathway for stroke and Parkinson's diseases therapy. Current Drug Targets - CNS & Neurological Disorders 2005, 4:63-67.
103. Kumari U., Tan E.K. LRRK2 in Parkinson's disease: genetic and clinical studies from patients. The FEBS Journal 2009, 276:6455-6463.
104. Kwok J.B., Hallupp M., Loy C.T., Chan D.K., Woo J., Mellick G.D., Buchanan D.D., Silburn P.A., Halliday G.M., Schofield P.R. GSK3B polymorphisms alter transcription and splicing in Parkinson's disease. Annals of Neurology 2005, 58:829-839.
105. Lee B.D., Shin J.H., VanKampen J., Petrucelli L., West A.B., Ko H.S., Lee Y.I., Maguire-Zeiss K.A., Bowers W.J., Federoff H.J., Dawson V.L., Dawson T.M. Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease. Nature Medicine 2010, 16:998-1000.
106. Lei P., Ayton S., Bush A.I., Adlard P.A. GSK-3 in Neurodegenerative Diseases. International Journal of Alzheimer's Disease 2011, 2011:189246.
107. Lev N., Ickowicz D., Barhum Y., Lev S., Melamed E., Offen D. DJ-1 protects against dopamine toxicity. Journal of Neural Transmission 2009, 116:151-160.
108. Li X., Moore D.J., Xiong Y., Dawson T.M., Dawson V.L. Reevaluation of phosphorylation sites in the Parkinson disease-associated leucine-rich repeat kinase 2. The Journal of Biological Chemistry 2010, 285:29569-29576.
109. Li X., Tan Y.C., Poulose S., Olanow C.W., Huang X.Y., Yue Z. Leucine-rich repeat kinase 2 (LRRK2)/PARK8 possesses GTPase activity that is altered in familial Parkinson's disease R1441C/G mutants. Journal of Neurochemistry 2007, 103:238-247.
110. Li Y., Liu W., Oo T.F., Wang L., Tang Y., Jackson-Lewis V., Zhou C., Geghman K., Bogdanov M., Przedborski S., Beal M.F., Burke R.E., Li C. Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's disease. Nature Neuroscience 2009, 12:826-828.
111. Li Y., Tomiyama H., Sato K., Hatano Y., Yoshino H., Atsumi M., Kitaguchi M., Sasaki S., Kawaguchi S., Miyajima H., Toda T., Mizuno Y., Hattori N. Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonism. Neurology 2005, 64:1955-1957.
112. Lilja L., Johansson J.U., Gromada J., Mandic S.A., Fried G., Berggren P.O., Bark C. Cyclin-dependent kinase 5 associated with p39 promotes Munc18-1 phosphorylation and Ca(2+)-dependent exocytosis. The Journal of Biological Chemistry 2004, 279:29534-29541.
113. Lindgren H.S., Ohlin K.E., Cenci M.A. Differential involvement of D1 and D2 dopamine receptors in L-DOPA-induced angiogenic activity in a rat model of Parkinson's disease. Neuropsychopharmacology 2009, 34:2477-2488.
114. Lin X., Parisiadou L., Gu X.L., Wang L., Shim H., Sun L., Xie C., Long C.X., Yang W.J., Ding J., Chen Z.Z., Gallant P.E., Tao-Cheng J.H., Rudow G., Troncoso J.C., Liu Z., Li Z., Cai H. Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson's-disease-related mutant alpha-synuclein. Neuron 2009, 64:807-827.
115. Liu S., Yu S., Hasegawa Y., Lapushin R., Xu H.J., Woodgett J.R., Mills G.B., Fang X. Glycogen synthase kinase 3beta is a negative regulator of growth factor-induced activation of the c-Jun N-terminal kinase. Journal of Biological Chemistry 2004, 279:51075-51081.
116. Liu Z., Hamamichi S., Lee B.D., Yang D., Ray A., Caldwell G.A., Caldwell K.A., Dawson T.M., Smith W.W., Dawson V.L. Inhibitors of LRRK2 kinase attenuate neurodegeneration and Parkinson-like phenotypes in Caenorhabditis elegans and Drosophila Parkinson's disease models. Human Molecular Genetics 2011, 20:3933-3942.
117. Lopes J.P., Agostinho P. Cdk5: multitasking between physiological and pathological conditions. Progress in Neurobiology 2011, 94:49-63.
118. Lucas J.J., Hernandez F., Gomez-Ramos P., Moran M.A., Hen R., Avila J. Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. The EMBO Journal 2001, 20:27-39.
119. MacLeod D., Dowman J., Hammond R., Leete T., Inoue K., Abeliovich A. The familial Parkinsonism gene LRRK2 regulates neurite process morphology. Neuron 2006, 52:587-593.
120. Manning G., Whyte D.B., Martinez R., Hunter T., Sudarsanam S. The protein kinase complement of the human genome. Science 2002, 298:1912-1934.
121. Matsuda N., Tanaka K. 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 2010, 19:1-9.
122. Matsui W., Kirchhausen T. Stabilization of clathrin coats by the core of the clathrin-associated protein complex AP-2. Biochemistry 1990, 29:10791-10798.
123. Mo J.S., Jung J., Yoon J.H., Hong J.A., Kim M.Y., Ann E.J., Seo M.S., Choi Y.H., Park H.S. DJ-1 modulates the p38 mitogen-activated protein kinase pathway through physical interaction with apoptosis signal-regulating kinase 1. Journal of Cellular Biochemistry 2010, 110:229-237.
124. Muqit M.M., Abou-Sleiman P.M., Saurin A.T., Harvey K., Gandhi S., Deas E., Eaton S., Payne Smith M.D., Venner K., Matilla A., Healy D.G., Gilks W.P., Lees A.J., Holton J., Revesz T., Parker P.J., Harvey R.J., Wood N.W., Latchman DS Altered cleavage and localization of PINK1 to aggresomes in the presence of proteasomal stress. Journal of Neurochemistry 2006, 98:156-169.
125. Naito Y., Shimizu H., Kasama T., Sato J., Tabara H., Okamoto A., Yabuta N., Nojima H. Cyclin G-associated kinase regulates protein phosphatase 2A by phosphorylation of its B'gamma subunit. Cell Cycle 2012, 11:604-616.
126. Nakamura S., Kawamoto Y., Nakano S., Akiguchi I., Kimura J. p35nck5a and cyclin-dependent kinase 5 colocalize in Lewy bodies of brains with Parkinson's disease. Acta Neuropathologica 1997, 94:153-157.
127. Nakaso K., Ito S., Nakashima K. Caffeine activates the PI3K/Akt pathway and prevents apoptotic cell death in a Parkinson's disease model of SH-SY5Y cells. Neuroscience Letters 2008, 432:146-150.
128. Nalls M.A., Plagnol V., Hernandez D.G., Sharma M., Sheerin U.M., Saad M., Simon-Sanchez J., Schulte C., Lesage S., Sveinbjornsdottir S., Stefansson K., Martinez M., Hardy J., Heutink P., Brice A., Gasser T., Singleton A.B., Wood N.W. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet 2011, 377:641-649.
129. Newhouse K., Hsuan S.L., Chang S.H., Cai B., Wang Y., Xia Z. Rotenone-induced apoptosis is mediated by p38 and JNK MAP kinases in human dopaminergic SH-SY5Y cells. Toxicological Sciences 2004, 79:137-146.
130. Nolen B., Yun C.Y., Wong C.F., McCammon J.A., Fu X.D., Ghosh G. The structure of Sky1p reveals a novel mechanism for constitutive activity. Nature Structural Biology 2001, 8:176-183.
131. Ohta E., Kawakami F., Kubo M., Obata F. LRRK2 directly phosphorylates Akt1 as a possible physiological substrate: impairment of the kinase activity by Parkinson's disease-associated mutations. FEBS Letters 2011, 585:2165-2170.
132. Owen D.J., Evans P.R. A structural explanation for the recognition of tyrosine-based endocytotic signals. Science 1998, 282:1327-1332.
133. Pan J., Qian J., Zhang Y., Ma J., Wang G., Xiao Q., Chen S., Ding J. Small peptide inhibitor of JNKs protects against MPTP-induced nigral dopaminergic injury via inhibiting the JNK-signaling pathway. Laboratory Investigation 2010, 90:156-167.
134. Pan J., Wang G., Yang H.Q., Hong Z., Xiao Q., Ren R.J., Zhou H.Y., Bai L., Chen S.D. 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 2007, 72:1607-1618.
135. Pan J., Xiao Q., Sheng C.Y., Hong Z., Yang H.Q., Wang G., Ding J.Q., Chen S.D. 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 2009, 54:418-425.
136. Pan T., Kondo S., Le W., Jankovic J. The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease. Brain 2008, 131:1969-1978.
137. Park J., Lee S.B., Lee S., Kim Y., Song S., Kim S., Bae E., Kim J., Shong M., Kim J.M., Chung J. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 2006, 441:1157-1161.
138. Pavese N., Moore R.Y., Scherfler C., Khan N.L., Hotton G., Quinn N.P., Bhatia K.P., Wood N.W., Brooks D.J., Lees A.J., Piccini P. In vivo assessment of brain monoamine systems in parkin gene carriers: a PET study. Experimental Neurology 2010, 222:120-124.
139. Pavon N., Martin A.B., Mendialdua A., Moratalla R. ERK phosphorylation and FosB expression are associated with L-DOPA-induced dyskinesia in hemiparkinsonian mice. Biological Psychiatry 2006, 59:64-74.
140. Pearson G., Robinson F., Beers Gibson T., Xu B.E., Karandikar M., Berman K., Cobb M.H. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocrine Reviews 2001, 22:153-183.
141. Pei D.S., Wang X.T., Liu Y., Sun Y.F., Guan Q.H., Wang W., Yan J.Z., Zong Y.Y., Xu T.L., Zhang G.Y. Neuroprotection against ischaemic brain injury by a GluR6-9c peptide containing the TAT protein transduction sequence. Brain 2006, 129:465-479.
142. Peng J., Mao X.O., Stevenson F.F., Hsu M., Andersen J.K. The herbicide paraquat induces dopaminergic nigral apoptosis through sustained activation of the JNK pathway. The Journal of Biological Chemistry 2004, 279:32626-32632.
143. Piccoli G., Condliffe S.B., Bauer M., Giesert F., Boldt K., De Astis S., Meixner A., Sarioglu H., Vogt-Weisenhorn D.M., Wurst W., Gloeckner C.J., Matteoli M., Sala C., Ueffing M. LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool. The Journal of Neuroscience 2011, 31:2225-2237.
144. Plowey E.D., Cherra S.J., Liu Y.J., Chu C.T. Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells. Journal of Neurochemistry 2008, 105:1048-1056.
145. Plun-Favreau H., Klupsch K., Moisoi N., Gandhi S., Kjaer S., Frith D., Harvey K., Deas E., Harvey R.J., McDonald N., Wood N.W., Martins L.M., Downward J. The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1. Nature Cell Biology 2007, 9:1243-1252.
146. Poole A.C., Thomas R.E., Yu S., Vincow E.S., Pallanck L. The mitochondrial fusion-promoting factor mitofusin is a substrate of the PINK1/parkin pathway. PLoS One 2010, 5:e10054.
147. Pridgeon J.W., Olzmann J.A., Chin L.S., Li L. PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1. PLoS Biology 2007, 5:e172.
148. Qin R., Li X., Li G., Tao L., Li Y., Sun J., Kang X., Chen J. Protection by tetrahydroxystilbene glucoside against neurotoxicity induced by MPP+: the involvement of PI3K/Akt pathway activation. Toxicology Letters 2011, 202:1-7.
149. Ramsden N., Perrin J., Ren Z., Lee B.D., Zinn N., Dawson V.L., Tam D., Bova M., Lang M., Drewes G., Bantscheff M., Bard F., Dawson T.M., Hopf C. Chemoproteomics-based design of potent LRRK2-selective lead compounds that attenuate Parkinson's disease-related toxicity in human neurons. ACS Chemical Biology 2011, 6:1021-1028.
150. Ran C., Westerlund M., Anvret A., Willows T., Sydow O., Galter D., Belin A.C. Genetic studies of the protein kinase AKT1 in Parkinson's disease. Neuroscience Letters 2011, 501:41-44.
151. Ray M.R., Wafa L.A., Cheng H., Snoek R., Fazli L., Gleave M., Rennie P.S. Cyclin G-associated kinase: a novel androgen receptor-interacting transcriptional coactivator that is overexpressed in hormone refractory prostate cancer. International Journal of Cancer 2006, 118:1108-1119.
152. Rhodes S.L., Sinsheimer J.S., Bordelon Y., Bronstein J.M., Ritz B. Replication of GWAS associations for GAK and MAPT in Parkinson's disease. Annals of Human Genetics 2011, 75:195-200. 10.1111/j. 1469-1809.2010.00616.x.
153. Rosales J.L., Lee K.Y. Extraneuronal roles of cyclin-dependent kinase 5. Bioessays 2006, 28:1023-1034.
154. Rosales J.L., Nodwell M.J., Johnston R.N., Lee K.Y. Cdk5/p25(nck5a) interaction with synaptic proteins in bovine brain. Journal of Cellular Biochemistry 2000, 78:151-159.
155. Rubinfeld B., Albert I., Porfiri E., Fiol C., Munemitsu S., Polakis P. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science 1996, 272:1023-1026.
156. Salminen A., Kaarniranta K., Haapasalo A., Soininen H., Hiltunen M. AMP-activated protein kinase: a potential player in Alzheimer's disease. Journal of Neurochemistry 2011, 118:460-474. 10.1111/j. 1471-4159.2011.07331.x.
157. Sanchez C., Perez M., Avila J. GSK3beta-mediated phosphorylation of the microtubule-associated protein 2C (MAP2C) prevents microtubule bundling. European Journal of Cell Biology 2000, 79:252-260.
158. Sanchez-Mora R.M., Arboleda H., Arboleda G. PINK1 overexpression protects against C2-ceramide-induced CAD cell death through the PI3K/AKT pathway. Journal of Molecular Neuroscience 2012, 47:582-594.
159. Santini E., Alcacer C., Cacciatore S., Heiman M., Herve D., Greengard P., Girault J.A., Valjent E., Fisone G. l-DOPA activates ERK signaling and phosphorylates histone H3 in the striatonigral medium spiny neurons of hemiparkinsonian mice. Journal of Neurochemistry 2009, 108:621-633.
160. Santini E., Sgambato-Faure V., Li Q., Savasta M., Dovero S., Fisone G., Bezard E. Distinct changes in cAMP and extracellular signal-regulated protein kinase signalling in l-DOPA-induced dyskinesia. PLoS One 2010, 5:e12322.
161. Santini E., Valjent E., Usiello A., Carta M., Borgkvist A., Girault J.A., Herve D., Greengard P., Fisone G. Critical involvement of cAMP/DARPP-32 and extracellular signal-regulated protein kinase signaling in l-DOPA-induced dyskinesia. The Journal of Neuroscience 2007, 27:6995-7005.
162. Sato J., Shimizu H., Kasama T., Yabuta N., Nojima H. GAK, a regulator of clathrin-mediated membrane trafficking, localizes not only in the cytoplasm but also in the nucleus. Genes Cells 2009, 14:627-641.
163. Schapira A.H. Etiology and pathogenesis of Parkinson disease. Neurologic Clinics 2009, 27:583-603.
164. Schubert S., Knoch K.P., Ouwendijk J., Mohammed S., Bodrov Y., Jager M., Altkruger A., Wegbrod C., Adams M.E., Kim Y., Froehner S.C., Jensen O.N., Kalaidzidis Y., Solimena M. beta2-Syntrophin is a Cdk5 substrate that restrains the motility of insulin secretory granules. PLoS One 2010, 5:e12929.
165. Shaw P.C., Davies A.F., Lau K.F., Garcia-Barcelo M., Waye M.M., Lovestone S., Miller C.C., Anderton B.H. Isolation and chromosomal mapping of human glycogen synthase kinase-3 alpha and -3 beta encoding genes. Genome 1998, 41:720-727.
166. Shimizu H., Nagamori I., Yabuta N., Nojima H. GAK, a regulator of clathrin-mediated membrane traffic, also controls centrosome integrity and chromosome congression. Journal of Cell Science 2009, 122:3145-3152.
167. Shimomura H., Imai A., Nashida T. Evidence for amylase release by cyclin-dependent kinase 5 in the rat parotid. Archives of Biochemistry and Biophysics 2011, 507:310-314.
168. Silva R.M., Kuan C.Y., Rakic P., Burke R.E. Mixed lineage kinase-c-jun N-terminal kinase signaling pathway: a new therapeutic target in Parkinson's disease. Movement Disorders 2005, 20:653-664.
169. Silvestri L., Caputo V., Bellacchio E., Atorino L., Dallapiccola B., Valente E.M., Casari G. Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Human Molecular Genetics 2005, 14:3477-3492.
170. Sim C.H., Lio D.S., Mok S.S., Masters C.L., Hill A.F., Culvenor J.G., Cheng H.C. 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 2006, 15:3251-3262.
171. Sitaram R.T., Cairney C.J., Grabowski P., Keith W.N., Hallberg B., Ljungberg B., Roos G. The PTEN regulator DJ-1 is associated with hTERT expression in clear cell renal cell carcinoma. International Journal of Cancer 2009, 125:783-790.
172. Smith P.D., Crocker S.J., Jackson-Lewis V., Jordan-Sciutto K.L., Hayley S., Mount M.P., O'Hare M.J., Callaghan S., Slack R.S., Przedborski S., Anisman H., Park D.S. 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 2003, 100:13650-13655.
173. Smith P.D., Mount M.P., Shree R., Callaghan S., Slack R.S., Anisman H., Vincent I., Wang X., Mao Z., Park D.S. 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 2006, 26:440-447.
174. Smith W.W., Pei Z., Jiang H., Dawson V.L., Dawson T.M., Ross C.A. Kinase activity of mutant LRRK2 mediates neuronal toxicity. Nature Neuroscience 2006, 9:1231-1233.
175. Song G., Ouyang G., Bao S. The activation of Akt/PKB signaling pathway and cell survival. Journal of Cellular and Molecular Medicine 2005, 9:59-71.
176. Songin M., Strosznajder J.B., Fital M., Kuter K., Kolasiewicz W., Nowak P., Ossowska K. Glycogen synthase kinase 3beta and its phosphorylated form (Y216) in the paraquat-induced model of parkinsonism. Neurotoxicity Research 2011, 19:162-171.
177. Soutar M.P., Kim W.Y., Williamson R., Peggie M., Hastie C.J., McLauchlan H., Snider W.D., Gordon-Weeks P.R., Sutherland C. Evidence that glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain. Journal of Neurochemistry 2010, 115:974-983.
178. Sundal C., Fujioka S., Uitti R.J., Wszolek Z.K. Autosomal dominant Parkinson's disease. Parkinsonism & Related Disorders 2012, 18(Suppl 1):S7-S10.
179. Susa M., Choy E., Liu X., Schwab J., Hornicek F.J., Mankin H., Duan Z. Cyclin G-associated kinase is necessary for osteosarcoma cell proliferation and receptor trafficking. Molecular Cancer Therapeutics 2010, 9:3342-3350.
180. Tanenbaum M.E., Vallenius T., Geers E.F., Greene L., Makela T.P., Medema R.H. Cyclin G-associated kinase promotes microtubule outgrowth from chromosomes during spindle assembly. Chromosoma 2010, 119:415-424.
181. Tian F.F., Zeng C., Ma Y.F., Guo T.H., Chen J.M., Chen Y., Cai X.F., Li F.R., Wang X.H., Huang W.J., Wang Y.Z. Potential roles of Cdk5/p35 and tau protein in hippocampal mossy fiber sprouting in the PTZ kindling model. Clinical Laboratory 2010, 56:127-136.
182. Timmons S., Coakley M.F., Moloney A.M., O' Neill C. Akt signal transduction dysfunction in Parkinson's disease. Neuroscience Letters 2009, 467:30-35.
183. Tomiyama H., Li Y., Yoshino H., Mizuno Y., Kubo S., Toda T., Hattori N. Mutation analysis for DJ-1 in sporadic and familial parkinsonism: screening strategy in parkinsonism. Neuroscience Letters 2009, 455:159-161.
184. Tomizawa K., Ohta J., Matsushita M., Moriwaki A., Li S.T., Takei K., Matsui H. Cdk5/p35 regulates neurotransmitter release through phosphorylation and downregulation of P/Q-type voltage-dependent calcium channel activity. The Journal of Neuroscience 2002, 22:2590-2597.
185. Tong Y., Shen J. alpha-Synuclein and LRRK2: partners in crime. Neuron 2009, 64:771-773.
186. Valente E.M., Abou-Sleiman P.M., Caputo V., Muqit M.M., Harvey K., Gispert S., Ali Z., Del Turco D., Bentivoglio A.R., Healy D.G., Albanese A., Nussbaum R., Gonzalez-Maldonado R., Deller T., Salvi S., Cortelli P., Gilks W.P., Latchman D.S., Harvey R.J., Dallapiccola B., Auburger G., Wood N.W. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 2004, 304:1158-1160.
187. Valente E.M., Bentivoglio A.R., Dixon P.H., Ferraris A., Ialongo T., Frontali M., Albanese A., Wood N.W. Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36. American Journal of Human Genetics 2001, 68:895-900.
188. Vasudevan K.M., Garraway L.A. AKT signaling in physiology and disease. Current Topics in Microbiology and Immunology 2010, 347:105-133.
189. Waak J., Weber S.S., Waldenmaier A., Gorner K., Alunni-Fabbroni M., Schell H., Vogt-Weisenhorn D., Pham T.T., Reumers V., Baekelandt V., Wurst W., Kahle P.J. Regulation of astrocyte inflammatory responses by the Parkinson's disease-associated gene DJ-1. The FASEB Journal 2009, 23:2478-2489.
190. Waldmeier P., Bozyczko-Coyne D., Williams M., Vaught J.L. 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 2006, 72:1197-1206.
191. Walker K., Olson M.F. Targeting Ras and Rho GTPases as opportunities for cancer therapeutics. Current Opinion in Genetics & Development 2005, 15:62-68.
192. Wang G., Qi C., Fan G.H., Zhou H.Y., Chen S.D. PACAP protects neuronal differentiated PC12 cells against the neurotoxicity induced by a mitochondrial complex I inhibitor, rotenone. FEBS Letters 2005, 579:4005-4011.
193. Wang L., Yang H.J., Xia Y.Y., Feng Z.W. Insulin-like growth factor 1 protects human neuroblastoma cells SH-EP1 against MPP+-induced apoptosis by AKT/GSK-3beta/JNK signaling. Apoptosis 2010, 15:1470-1479.
194. Wang L.H., Johnson E.M. Mixed lineage kinase inhibitor CEP-1347 fails to delay disability in early Parkinson disease. Neurology 2008, 71:462. (author reply 462-3).
195. Wang W., Yang Y., Ying C., Li W., Ruan H., Zhu X., You Y., Han Y., Chen R., Wang Y., Li M. Inhibition of glycogen synthase kinase-3beta protects dopaminergic neurons from MPTP toxicity. Neuropharmacology 2007, 52:1678-1684.
196. Wang Y., Zhang Y., Wei Z., Li H., Zhou H., Zhang Z., Zhang Z. 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 2009, 285:172-177.
197. Wang Z., Liu J., Chen S., Wang Y., Cao L., Zhang Y., Kang W., Li H., Gui Y., Chen S., Ding J. DJ-1 modulates the expression of Cu/Zn-superoxide dismutase-1 through the Erk1/2-Elk1 pathway in neuroprotection. Annals of Neurology 2011, 70:591-599. 10.1002/ana.22514.
198. Wei F.Y., Nagashima K., Ohshima T., Saheki Y., Lu Y.F., Matsushita M., Yamada Y., Mikoshiba K., Seino Y., Matsui H., Tomizawa K. Cdk5-dependent regulation of glucose-stimulated insulin secretion. Nature Medicine 2005, 11:1104-1108.
199. Weng Y.H., Chou Y.H., Wu W.S., Lin K.J., Chang H.C., Yen T.C., Chen R.S., Wey S.P., Lu C.S. PINK1 mutation in Taiwanese early-onset parkinsonism: clinical, genetic, and dopamine transporter studies. Journal of Neurology 2007, 254:1347-1355.
200. Wilms H., Rosenstiel P., Sievers J., Deuschl G., Zecca L., Lucius R. 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 2003, 17:500-502.
201. Wong A.S., Lee R.H., Cheung A.Y., Yeung P.K., Chung S.K., Cheung Z.H., Ip N.Y. Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson's disease. Nature Cell Biology 2011, 13:568-579.
202. Woodgett J.R. Molecular cloning and expression of glycogen synthase kinase-3/factor A. The EMBO Journal 1990, 9:2431-2438.
203. Xiong Y., Coombes C.E., Kilaru A., Li X., Gitler A.D., Bowers W.J., Dawson V.L., Dawson T.M., Moore D.J. GTPase activity plays a key role in the pathobiology of LRRK2. PLoS Genetics 2010, 6:e1000902.
204. Xiromerisiou G., Hadjigeorgiou G.M., Papadimitriou A., Katsarogiannis E., Gourbali V., Singleton A.B. Association between AKT1 gene and Parkinson's disease: a protective haplotype. Neuroscience Letters 2008, 436:232-234.
205. Yang Y., Gehrke S., Haque M.E., Imai Y., Kosek J., Yang L., Beal M.F., Nishimura I., Wakamatsu K., Ito S., Takahashi R., Lu B. 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 2005, 102:13670-13675.
206. Yasuda S., Sugiura H., Tanaka H., Takigami S., Yamagata K. p38 MAP kinase inhibitors as potential therapeutic drugs for neural diseases. Central Nervous System Agents in Medicinal Chemistry 2011, 11:45-59.
207. Yong H.Y., Koh M.S., Moon A. The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer. Expert Opinion on Investigational Drugs 2009, 18:1893-1905.
208. Yun H., Heo H.Y., Kim H.H., DooKim N., Seol W. 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 2011, 21:2953-2957.
209. Yun J., Cao J.H., Dodson M.W., Clark I.E., Kapahi P., Chowdhury R.B., Guo M. Loss-of-function analysis suggests that Omi/HtrA2 is not an essential component of the PINK1/PARKIN pathway in vivo. The Journal of Neuroscience 2008, 28:14500-14510.
210. Zawada W.M., Meintzer M.K., Rao P., Marotti J., Wang X., Esplen J.E., Clarkson E.D., Freed C.R., Heidenreich K.A. Inhibitors of p38 MAP kinase increase the survival of transplanted dopamine neurons. Brain Research 2001, 891:185-196.
211. Zhang L., Gjoerup O., Roberts T.M. 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 2004, 101:10296-10301.
212. Zimprich A. Genetics of Parkinson's disease and essential tremor. Current Opinion in Neurology 2011, 24:318-323.