Fyn kinase regulates microglial neuroinflammatory responses in cell culture and animal models of parkinson’s disease

Journal of Neuroscience

Volumn 35, Issue 27, 2015, Pages 10058-10077

  Panicker, Nikhil ^a   Saminathan, Hariharan ^a   Jin, Huajun ^a   Neal, Matthew ^a   Harischandra, Dilshan S ^a   Gordon, Richard ^a   Kanthasamy, Kavin ^a   Lawana, Vivek ^a   Sarkar, Souvarish ^a   Luo, Jie ^a   Anantharam, Vellareddy ^a   Kanthasamy, Anumantha G ^a   Kanthasamy, Arthi ^a  

^a IOWA STATE UNIVERSITY   (United States)

Author keywords

Fyn; Kinase; Microglia; Neuroinflammation; Parkinson s disease; Phosphorylation

Indexed keywords

1, 2, 3, 6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; BETA ACTIN; ETANERCEPT; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 12; INTERLEUKIN 6; LAMIN B; LIPOPOLYSACCHARIDE; LUCIFERASE; MITOGEN ACTIVATED PROTEIN KINASE; NITRIC OXIDE; OXIDOPAMINE; PROTEIN KINASE FYN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 2; SMALL INTERFERING RNA; TUBULIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; CYTOKINE; FYN PROTEIN, MOUSE; PROTEIN KINASE C DELTA; TYROSINE; TYROSINE 3 MONOOXYGENASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL CULTURE; CONFOCAL MICROSCOPY; CONTROLLED STUDY; CYTOPLASM; GENETIC TRANSFECTION; IMMUNOASSAY; IMMUNOBLOTTING; IMMUNOCYTOCHEMISTRY; IMMUNOFLUORESCENCE; IMMUNOHISTOCHEMISTRY; IMMUNOPRECIPITATION; MICROGLIA; MOUSE; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; UPREGULATION; WESTERN BLOTTING; ANIMAL; C57BL MOUSE; CELL FRACTIONATION; COMPLICATION; DISEASE MODEL; DRUG EFFECTS; ENCEPHALITIS; GENETICS; KNOCKOUT MOUSE; METABOLISM; PHOSPHORYLATION; PROCEDURES; ULTRASTRUCTURE;

ANIMALS; CELL FRACTIONATION; CELLS, CULTURED; CYTOKINES; DISEASE MODELS, ANIMAL; ENCEPHALITIS; LIPOPOLYSACCHARIDES; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICROGLIA; NITRIC OXIDE; OXIDOPAMINE; PARKINSON DISEASE; PHOSPHORYLATION; PROTEIN KINASE C-DELTA; PROTO-ONCOGENE PROTEINS C-FYN; TUMOR NECROSIS FACTOR-ALPHA; TYROSINE; TYROSINE 3-MONOOXYGENASE;

EID: 84936881452     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.0302-15.2015     Document Type: Article

References (75)

1. Anantharam V, Kitazawa M, Wagner J, Kaul S, Kanthasamy AG (2002) Caspase-3-dependent proteolytic cleavage of protein kinase C+ is essential for oxidative stress-mediated dopaminergic cell death after exposure to methylcyclopentadienyl manganese tricarbonyl. J Neurosci 22: 1738-1751. Medline.
2. Barcia C, Ros CM, Annese V, Carrillo-de Sauvage MA, Ros-Bernal F, Gomez A, Yuste JE, Campuzano CM, de Pablos V, Fernandez-Villalba E, Herrero MT (2012) ROCK/Cdc42-mediated microglial motility and gliapse formation lead to phagocytosis of degenerating dopaminergic neurons in vivo. Sci Rep 2: 809. CrossRef Medline.
3. Barcia C, Ros CM, Ros-Bernal F, Gómez A, Annese V, Carrillo-de Sauvage MA, Yuste JE, Campuzano CM, de Pablos V, Fernández-Villalba E, Herrero MT (2013) Persistent phagocytic characteristics of microglia in the substantia nigra of long-term parkinsonian macaques. J Neuroimmunol 261: 60-66. CrossRef Medline.
4. Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8: 57-69. CrossRef Medline.
5. Bohnen NI, Frey KA, Studenski S, Kotagal V, Koeppe RA, Constantine GM, Scott PJ, Albin RL, Müller ML (2014) Extra-nigral pathological conditions are common in Parkinson's disease with freezing of gait: an in vivo positron emission tomography study. Mov Disord 29: 1118-1124. CrossRef Medline.
6. Burguillos MA, Deierborg T, Kavanagh E, Persson A, Hajji N, Garcia-Quintanilla A, Cano J, Brundin P, Englund E, Venero JL, Joseph B (2011) Caspase signalling controls microglia activation and neurotoxicity. Nature 472: 319-324. CrossRef Medline.
7. Carson MJ (2002) Microglia as liaisons between the immune and central nervous systems: functional implications for multiple sclerosis. Glia 40: 218-231. CrossRef Medline.
8. Chaudhuri KR, Healy DG, Schapira AH (2006) Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol 5: 235-245. CrossRef Medline.
9. Choi HB, Ryu JK, Kim SU, McLarnon JG (2007) Modulation of the purinergic P2X7 receptor attenuates lipopolysaccharide-mediated microglial activation and neuronal damage in inflamed brain. J Neurosci 27: 4957-4968. CrossRef Medline.
10. Crotti A, Benner C, Kerman BE, Gosselin D, Lagier-Tourenne C, Zuccato C, Cattaneo E, Gage FH, Cleveland DW, Glass CK (2014) Mutant Huntingtin promotes autonomous microglia activation via myeloid lineagedetermining factors. Nat Neurosci 17: 513-521. CrossRef Medline.
11. Dey N, Crosswell HE, De P, Parsons R, Peng Q, Su JD, Durden DL (2008) The protein phosphatase activity of PTEN regulates SRC family kinases and controls glioma migration. Cancer Res 68: 1862-1871. CrossRef Medline.
12. Dunah AW, Sirianni AC, Fienberg AA, Bastia E, Schwarzschild MA, Standaert DG (2004) Dopamine D1-dependent trafficking of striatal N-methyl-Daspartate glutamate receptors requires Fyn protein tyrosine kinase but not DARPP-32. Mol Pharmacol 65: 121-129. CrossRef Medline.
13. El Benna J, Faust RP, Johnson JL, Babior BM (1996) Phosphorylation of the respiratory burst oxidase subunit p47phox as determined by twodimensional phosphopeptide mapping: phosphorylation by protein kinase C, protein kinase A, and a mitogen-activated protein kinase. J Biol Chem 271: 6374-6378. CrossRef Medline.
14. Engelmann S, Togni M, Thielitz A, Reichardt P, Kliche S, Reinhold D, Schraven B, Reinhold A (2013) T cell-independent modulation of experimental autoimmune encephalomyelitis in ADAP-deficient mice. J Immunol 191: 4950-4959. CrossRef Medline.
15. Finberg RW, Yim C, Yan J, Cao LC, Mandell L, Kurt-Jones EA (2012) Phosphorylated Toll-like receptor 2 interacts with Fyn and cross talks with the phosphorylation-independent TLR2-signaling pathway. Open Immunol J 5: 36-45. CrossRef.
16. Gao HM, Zhou H, Zhang F, Wilson BC, Kam W, Hong JS (2011) HMGB1 acts on microglia Mac1 to mediate chronic neuroinflammation that drives progressive neurodegeneration. J Neurosci 31: 1081-1092. CrossRef Medline.
17. Ghosh A, Roy A, Liu X, Kordower JH, Mufson EJ, Hartley DM, Ghosh S, Mosley RL, Gendelman HE, Pahan K (2007) Selective inhibition of NFkappaB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease. Proc Natl Acad Sci U S A 104: 18754-18759. CrossRef Medline.
18. Ghosh A, Chandran K, Kalivendi SV, Joseph J, Antholine WE, Hillard CJ, Kanthasamy A, Kalyanaraman B (2010) Neuroprotection by a mitochondriatargeted drug in a Parkinson's disease model. Free Radic Biol Med 49: 1674-1684. CrossRef Medline.
19. Ghosh A, Saminathan H, Kanthasamy A, Anantharam V, Jin H, Sondarva G, Harischandra DS, Qian Z, Rana A, Kanthasamy AG (2013) The peptidyl-prolyl isomerase Pin1 up-regulation and proapoptotic function in dopaminergic neurons: relevance to the pathogenesis of Parkinson disease. J Biol Chem 288: 21955-21971. CrossRef Medline.
20. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140: 918-934. CrossRef Medline.
21. Gomez G, Gonzalez-Espinosa C, Odom S, Baez G, Cid ME, Ryan JJ, Rivera J (2005) Impaired Fc+RI-dependent gene expression and defective eicosanoid and cytokine production as a consequence of Fyn deficiency in mast cells. J Immunol 175: 7602-7610. CrossRef Medline.
22. Gong P, Angelini DJ, Yang S, Xia G, Cross AS, Mann D, Bannerman DD, Vogel SN, Goldblum SE (2008) TLR4 signaling is coupled to SRC family kinase activation, tyrosine phosphorylation of zonula adherens proteins, and opening of the paracellular pathway in human lung microvascular endothelia. J Biol Chem 283: 13437-13449. CrossRef Medline.
23. Gordon R, Hogan CE, Neal ML, Anantharam V, Kanthasamy AG, Kanthasamy A (2011) A simple magnetic separation method for high-yield isolation of pure primary microglia. J Neurosci Methods 194: 287-296. CrossRef Medline.
24. Gordon R, Anantharam V, Kanthasamy AG, Kanthasamy A (2012) Proteolytic activation of proapoptotic kinase protein kinase C+ by tumor necrosis factor alpha death receptor signaling in dopaminergic neurons during neuroinflammation. J Neuroinflammation 9: 82. CrossRef Medline.
25. Harischandra DS, Kondru N, Martin DP, Kanthasamy A, Jin H, Anantharam V, Kanthasamy AG (2014) Role of proteolytic activation of protein ki-nase C+ in the pathogenesis of prion disease. Prion 8: 143-153. CrossRef Medline.
26. Hayden MS, Ghosh S (2004) Signaling to NF-kappaB. Genes Dev 18: 2195-2224. CrossRef Medline.
27. Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan WB, Julius D (2006) The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 9: 1512-1519. CrossRef Medline.
28. Henn A, Lund S, Hedtjärn M, Schrattenholz A, Pörzgen P, Leist M (2009) The suitability of BV2 cells as alternative model system for primary microglia cultures or for animal experiments examining brain inflammation. ALTEX 26: 83-94. Medline.
29. Hickman SE, Kingery ND, Ohsumi TK, Borowsky ML, Wang LC, Means TK, El Khoury J (2013) The microglial sensome revealed by direct RNA sequencing. Nat Neurosci 16: 1896-1905. CrossRef Medline.
30. Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson's disease: a target for neuroprotection? Lancet Neurol 8: 382-397. CrossRef Medline.
31. Hu X, Zhang D, Pang H, Caudle WM, Li Y, Gao H, Liu Y, Qian L, Wilson B, Di Monte DA, Ali SF, Zhang J, Block ML, Hong JS (2008) Macrophage antigen complex-1 mediates reactive microgliosis and progressive dopaminergic neurodegeneration in the MPTP model of Parkinson's disease. J Immunol 181: 7194-7204. CrossRef Medline.
32. Imamura K, Hishikawa N, Sawada M, Nagatsu T, Yoshida M, Hashizume Y (2003) Distribution of major histocompatibility complex class IIpositive microglia and cytokine profile of Parkinson's disease brains. Acta Neuropathol 106: 518-526. CrossRef Medline.
33. Jenner P, Olanow CW (2006) The pathogenesis of cell death in Parkinson's disease. Neurology 66: S24-S36. CrossRef Medline.
34. Jin H, Kanthasamy A, Anantharam V, Rana A, Kanthasamy AG (2011a) Transcriptional regulation of pro-apoptotic protein kinase C+: implications for oxidative stress-induced neuronal cell death. J Biol Chem 286: 19840-19859. CrossRef Medline.
35. Jin H, Kanthasamy A, Ghosh A, Yang Y, Anantharam V, Kanthasamy AG (2011b) α-Synuclein negatively regulates protein kinaseC+ expression to suppress apoptosis in dopaminergic neurons by reducing p300 histone acetyltransferase activity. J Neurosci 31: 2035-2051. CrossRef Medline.
36. Jin H, Kanthasamy A, Harischandra DS, Kondru N, Ghosh A, Panicker N, Anantharam V, Rana A, Kanthasamy AG (2014) Histone hyperacetylation up-regulates protein kinase C+ in dopaminergic neurons to induce cell death: relevance to epigenetic mechanisms of neurodegeneration in Parkinson disease. J Biol Chem 289: 34743-34767. CrossRef Medline.
37. Kaspar JW, Jaiswal AK (2011) Tyrosine phosphorylation controls nuclear export of Fyn, allowing Nrf2 activation of cytoprotective gene expression. FASEB J 25: 1076-1087. CrossRef Medline.
38. Kaul S, Kanthasamy A, Kitazawa M, Anantharam V, Kanthasamy AG (2003) Caspase-3 dependent proteolytic activation of protein kinaseC+ mediates and regulates 1-methyl-4-phenylpyridinium (MPP+)-induced apoptotic cell death in dopaminergic cells: relevance to oxidative stress in dopaminergic degeneration. Eur J Neurosci 18: 1387-1401. CrossRef Medline.
39. Kaul S, Anantharam V, Yang Y, Choi CJ, Kanthasamy A, Kanthasamy AG (2005) Tyrosine phosphorylation regulates the proteolytic activation of protein kinase C+ in dopaminergic neuronal cells. J Biol Chem 280: 28721-28730. CrossRef Medline.
40. Kim C, Ho DH, Suk JE, You S, Michael S, Kang J, Joong Lee S, Masliah E, Hwang D, Lee HJ, Lee SJ (2013a) Neuron-released oligomeric alphasynuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nat Commun 4: 1562. CrossRef Medline.
41. Kim JH, Choi DJ, Jeong HK, Kim J, Kim DW, Choi SY, Park SM, Suh YH, Jou I, Joe EH (2013b) DJ-1 facilitates the interaction between STAT1 and its phosphatase, SHP-1, in brain microglia and astrocytes: a novel antiinflammatory function of DJ-1. Neurobiol Dis 60: 1-10. CrossRef Medline.
42. Kim YS, Choi DH, Block ML, Lorenzl S, Yang L, Kim YJ, Sugama S, Cho BP, Hwang O, Browne SE, Kim SY, Hong JS, Beal MF, Joh TH (2007) A pivotal role of matrix metalloproteinase-3 activity in dopaminergic neuronal degeneration via microglial activation. FASEB J 21: 179-187. CrossRef Medline.
43. Koistinaho M, Koistinaho J (2002) Role of p38 and p44/42 mitogenactivated protein kinases in microglia. Glia 40: 175-183. CrossRef Medline.
44. Kouadir M, Yang L, Tan R, Shi F, Lu Y, Zhang S, Yin X, Zhou X, Zhao D (2012) CD36 participates in PrP106-126-induced activation of microglia. PLoS One 7: e30756. CrossRef Medline.
45. Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL, Wals P, Zhang C, Finch CE, Krafft GA, Klein WL (1998) Diffusible, nonfibrillar ligands derived from Ab1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci U S A 95: 6448-6453. CrossRef Medline.
46. Larson M, Sherman MA, Amar F, Nuvolone M, Schneider JA, Bennett DA, Aguzzi A, Lesné SE (2012) The complex PrP(c)-Fyn couples human oligomeric Abeta with pathological tau changes in Alzheimer's disease. J Neurosci 32: 16857-16871. CrossRef Medline.
47. Lastres-Becker I, Ulusoy A, Innamorato NG, Sahin G, Rábano A, Kirik D, Cuadrado A (2012) α-Synuclein expression and Nrf2 deficiency cooperate to aggravate protein aggregation, neuronal death and inflammation in early-stage Parkinson's disease. Hum Mol Genet 21: 3173-3192. CrossRef Medline.
48. Latchoumycandane C, Anantharam V, Jin H, Kanthasamy A, Kanthasamy A (2011) Dopaminergic neurotoxicant 6-OHDA induces oxidative damage through proteolytic activation of PKC+ in cell culture and animal models of Parkinson's disease. Toxicol Appl Pharmacol 256: 314-323. CrossRef Medline.
49. Lee S, Nam Y, Koo JY, Lim D, Park J, Ock J, Kim J, Suk K, Park SB (2014) A small molecule binding HMGB1 and HMGB2 inhibits microgliamediated neuroinflammation. Nat Chem Biol 10: 1055-1060. CrossRef Medline.
50. Levy OA, Malagelada C, Greene LA (2009) Cell death pathways in Parkinson's disease: proximal triggers, distal effectors, and final steps. Apoptosis 14: 478-500. CrossRef Medline.
51. Moore KJ, El Khoury J, Medeiros LA, Terada K, Geula C, Luster AD, Freeman MW (2002) A CD36-initiated signaling cascade mediates inflammatory effects of beta-amyloid. J Biol Chem 277: 47373-47379. CrossRef Medline.
52. OlanowCW (2007) The pathogenesis of cell death in Parkinson's disease-2007. Mov Disord 22 [Suppl 17]: S335-S342.
53. Olson JK, Miller SD (2004) Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J Immunol 173: 3916-3924. CrossRef Medline.
54. Palacios EH, Weiss A (2004) Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation. Oncogene 23: 7990-8000. CrossRef Medline.
55. Parameswaran N, Patial S (2010) Tumor necrosis factor-β signaling in macrophages. Crit Rev Eukaryot Gene Expr 20: 87-103. CrossRef Medline.
56. Przedborski S (2005) Pathogenesis of nigral cell death in Parkinson's disease. Parkinsonism Relat Disord 11 [Suppl 1]: S3-S7.
57. Przedborski S, Tieu K, Perier C, Vila M (2004) MPTP as a mitochondrial neurotoxic model of Parkinson's disease. J Bioenerg Biomembr 36: 375-379. CrossRef Medline.
58. Puschmann A (2013) Monogenic Parkinson's disease and parkinsonism: clinical phenotypes and frequencies of known mutations. Parkinsonism Relat Disord 19: 407-415. CrossRef Medline.
59. Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT (2007) Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55: 453-462. CrossRef Medline.
60. Rajasekaran K, Kumar P, Schuldt KM, Peterson EJ, Vanhaesebroeck B, Dixit V, Thakar MS, Malarkannan S (2013) Signaling by Fyn-ADAP via the Carma1-Bcl-10-MAP3K7 signalosome exclusively regulates inflammatory cytokine production in NK cells. Nat Immunol 14: 1127-1136. CrossRef Medline.
61. Reed-Geaghan EG, Savage JC, Hise AG, Landreth GE (2009) CD14 and tolllike receptors 2 and 4 are required for fibrillar A+-stimulated microglial activation. J Neurosci 29: 11982-11992. CrossRef Medline.
62. Saminathan H, Asaithambi A, Anantharam V, Kanthasamy AG, Kanthasamy A (2011) Environmental neurotoxic pesticide dieldrin activates a non receptor tyrosine kinase to promote PKC+-mediated dopaminergic apoptosis in a dopaminergic neuronal cell model. Neurotoxicology 32: 567-577. CrossRef Medline.
63. Sperber BR, Boyle-Walsh EA, Engleka MJ, Gadue P, Peterson AC, Stein PL, Scherer SS, McMorris FA (2001) A unique role for Fyn in CNS myelination. J Neurosci 21: 2039-2047. Medline.
64. Sriram K, Matheson JM, Benkovic SA, Miller DB, Luster MI, O'Callaghan JP (2006) Deficiency of TNF receptors suppresses microglial activation and alters the susceptibility of brain regions to MPTP-induced neurotoxicity: role of TNF-alpha. FASEB J 20: 670-682. CrossRef Medline.
65. Steinberg SF (2004) Distinctive activation mechanisms and functions for protein kinase C+. Biochem J 384: 449-459. CrossRef Medline.
66. Stott SR, Barker RA (2014) Time course of dopamine neuron loss and glial response in the 6-OHDA striatal mouse model of Parkinson's disease. Eur J Neurosci 39: 1042-1056. CrossRef Medline.
67. Stuart LM, Bell SA, Stewart CR, Silver JM, Richard J, Goss JL, Tseng AA, Zhang A, El Khoury JB, Moore KJ (2007) CD36 signals to the actin cytoskeleton and regulates microglial migration via a p130Cas complex. J Biol Chem 282: 27392-27401. CrossRef Medline.
68. Su X, Maguire-Zeiss KA, Giuliano R, Prifti L, Venkatesh K, Federoff HJ (2008) Synuclein activates microglia in a model of Parkinson's disease. Neurobiol Aging 29: 1690-1701. CrossRef Medline.
69. Tansey MG, Goldberg MS (2010) Neuroinflammation in Parkinson's disease: its role in neuronal death and implications for therapeutic intervention. Neurobiol Dis 37: 510-518. CrossRef Medline.
70. Um JW, Nygaard HB, Heiss JK, Kostylev MA, Stagi M, Vortmeyer A, Wisniewski T, Gunther EC, StrittmatterSM (2012) Alzheimer amyloid-beta oligomer bound to postsynaptic prion protein activates Fyn to impair neurons. Nat Neurosci 15: 1227-1235. CrossRef Medline.
71. Virgone-Carlotta A, Uhlrich J, Akram MN, Ressnikoff D, Chrétien F, Domenget C, Gherardi R, Despars G, Jurdic P, Honnorat J, Nataf S, TouretM (2013) Mapping and kinetics of microglia/neuron cell-to-cell contacts in the 6-OHDA murine model of Parkinson's disease. Glia 61: 1645-1658. CrossRef Medline.
72. Wake H, Lee PR, Fields RD (2011) Control of local protein synthesis and initial events in myelination by action potentials. Science 333: 1647-1651. CrossRef Medline.
73. Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, Choi DK, Ischiropoulos H, Przedborski S (2002) Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci 22: 1763-1771. Medline.
74. Wu DC, Teismann P, Tieu K, Vila M, Jackson-Lewis V, Ischiropoulos H, Przedborski S (2003) NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine model of Parkinson's disease. Proc Natl Acad Sci U S A 100: 6145-6150. CrossRef Medline.
75. Zhang D, Anantharam V, Kanthasamy A, Kanthasamy AG (2007) Neuroprotective effect of protein kinase C+inhibitor rottlerin in cell culture and animal models of Parkinson's disease. J Pharmacol Exp Ther 322: 913-922. CrossRef Medline.