The Library
The role of p38 MAPK and its substrates in neuronal plasticity and neurodegenerative disease
Tools
Corrêa, Sônia A. L. and Eales, Katherine L.. (2012) The role of p38 MAPK and its substrates in neuronal plasticity and neurodegenerative disease. Journal of Signal Transduction, Vol.2012 . Article no. 649079. ISSN 2090-1739
|
Text
WRAP_Correa_649079.pdf - Published Version Download (767Kb) | Preview |
Official URL: http://dx.doi.org/10.1155/2012/649079
Abstract
A significant amount of evidence suggests that the p38-mitogen-activated protein kinase (MAPK) signalling cascade plays a crucial role in synaptic plasticity and in neurodegenerative diseases. In this review we will discuss the cellular localisation and activation of p38 MAPK and the recent advances on the molecular and cellular mechanisms of its substrates: MAPKAPK 2 (MK2) and tau protein. In particular we will focus our attention on the understanding of the p38 MAPK-MK2 and p38 MAPK-tau activation axis in controlling neuroinflammation, actin remodelling and tau hyperphosphorylation, processes that are thought to be involved in normal ageing as well as in neurodegenerative diseases. We will also give some insight into how elucidating the precise role of p38 MAPK-MK2 and p38 MAPK-tau signalling cascades may help to identify novel therapeutic targets to slow down the symptoms observed in neurodegenerative diseases such as Alzheimer's and Parkinson's disease.
| Item Type: | Journal Article |
|---|---|
| Subjects: | Q Science > QP Physiology |
| Divisions: | Faculty of Science > Life Sciences (2010- ) |
| Library of Congress Subject Headings (LCSH): | Nervous system -- Degeneration, Neuroplasticity, Protein kinases |
| Journal or Publication Title: | Journal of Signal Transduction |
| Publisher: | Hindawi Publishing Corporation |
| ISSN: | 2090-1739 |
| Date: | 2012 |
| Volume: | Vol.2012 |
| Page Range: | Article no. 649079 |
| Identification Number: | 10.1155/2012/649079 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Open Access |
| Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), University of Warwick |
| Grant number: | BB/H018344/1 (BBSRC), BB/J02127X/1 (BBSRC) |
| References: | [1] A. Cuadrado and A. Nebreda, “Mechanisms and functions of p38 MAPK signalling,” Biochemical Journal, vol. 429, no. 3, pp. 403–417, 2010. [2] Z. Wang, P. C. Harkins, R. J. Ulevitch, J. Han, M. H. Cobb, and E. J. Goldsmith, “The structure of mitogen-activated protein kinase p38 at 2.1-°a resolution,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 6, pp. 2327–2332, 1997. [3] R. Ben-Levy, S. Hooper, R. Wilson, H. F. Paterson, and C. J. Marshall, “Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2,” Current Biology, vol. 8, no. 19, pp. 1049–1057, 1998. [4] T. Tomida, M. Takekawa, P. O’Grady, and H. Saito, “Stimulus- specific distinctions in spatial and temporal dynamics of stress-activated protein kinase kinase kinases revealed by a fluorescence resonance energy transfer biosensor,” Molecular and Cellular Biology, vol. 29, no. 22, pp. 6117–6127, 2009. [5] A. Cuenda and S. Rousseau, “P38 MAP-kinases pathway regulation, function and role in human diseases,” Biochimica et Biophysica Acta, vol. 1773, no. 8, pp. 1358–1375, 2007. [6] A. Risco and A. Cuenda, “New insights into the p38 γ and p38 δ MAPK pathways,” Journal of Signal Transduction, vol. 2012, Article ID 520289, 8 pages, 2012. [7] L. Munoz and A. J. Ammit, “Targeting p38 MAPK pathway for the treatment of Alzheimer’s disease,” Neuropharmacology, vol. 58, no. 3, pp. 561–568, 2010. [8] J. D. English and J. D. Sweatt, “A requirement for the mitogen- activated protein kinase cascade in hippocampal long term potentiation,” The Journal of Biological Chemistry, vol. 272, no. 31, pp. 19103–19106, 1997. [9] G. M. Thomas and R. L. Huganir, “MAPK cascade signalling and synaptic plasticity,” Nature Reviews Neuroscience, vol. 5, no. 3, pp. 173–183, 2004. [10] V. A. Beardmore, H. J. Hinton, C. Eftychi et al., “Generation and characterization of p38β (MAPK11) gene-targeted mice,” Molecular and Cellular Biology, vol. 25, no. 23, pp. 10454–10464, 2005. [11] S. H. Lee, J. Park, Y. Che, P. L. Han, and J. K. Lee, “Constitutive activity and differential localization of p38α and p38β MAPKs in adult mouse brain,” Journal of Neuroscience Research, vol. 60, no. 5, pp. 623–631, 2000. [12] J. Bain, L. Plater, M. Elliott et al., “The selectivity of protein kinase inhibitors: a further update,” Biochemical Journal, vol. 408, no. 3, pp. 297–315, 2007. [13] J. Da Silva, B. Pierrat, J. L.Mary, andW. Lesslauer, “Blockade of p38 mitogen-activated protein kinase pathway inhibits inducible nitric-oxide synthase expression in mouse astrocytes,” The Journal of Biological Chemistry, vol. 272, no. 45, pp. 28373–28380, 1997. [14] J. I. Kakimura, Y. Kitamura, K. Takata et al., “Microglial activation and amyloid-β clearance induced by exogenous heatshock proteins,” FASEB Journal, vol. 16, no. 6, pp. 601–603, 2002. [15] C. Richter-Landsberg, A.Wyttenbach, and A. P. Arrigo, “The role of heat shock proteins during neurodegeneration in Alzheimer’s, Parkinson’s and Huntington’s disease,” in Heat Shock Proteins inNeural Cells, pp. 81–99, Springer, New York, NY, USA, 2009. [16] G. L. Collingridge, J. T. R. Isaac, and Y. T. Wang, “Receptor trafficking and synaptic plasticity,” Nature Reviews Neuroscience, vol. 5, no. 12, pp. 952–962, 2004. [17] J. D. Shepherd and R. L. Huganir, “The cell biology of synaptic plasticity: AMPA receptor trafficking,” Annual Review of Cell and Developmental Biology, vol. 23, pp. 613–643, 2007. [18] G. L. Collingridge, S. Peineau, J. G. Howland, and Y. T.Wang, “Long-term depression in the CNS,” Nature Reviews Neuroscience, vol. 11, no. 7, pp. 459–473, 2010. [19] C. M. Gladding, S. M. Fitzjohn, and E. Moln´ar, “Metabotropic glutamate receptor-mediated long-term depression: molecular mechanisms,” Pharmacological Reviews, vol. 61, no. 4, pp. 395–412, 2009. [20] P. R. Moult, S. A. L. Corrˆea, G. L. Collingridge, S. M. Fitzjohn, and Z. I. Bashir, “Co-activation of p38 mitogenactivated protein kinase and protein tyrosine phosphatase underlies metabotropic glutamate receptor-dependent longterm depression,” Journal of Physiology, vol. 586, no. 10, pp. 2499–2510, 2008. [21] J. Arthur, “MSK activation and physiological roles,” Frontiers in Bioscience, vol. 13, pp. 5866–5879, 2008. [22] B. G. Frenguelli and S. A. L. Corrˆea, “Regulation and role of MSK in the mammalian brain,” in MSKs, J. S. C. Arthur, Ed., Landes Bioscience, Austin, Tex, USA, 2012. [23] C. C. Huang, J. L. You, M. Y. Wu, and K. S. Hsu, “Rap1- induced p38 mitogen-activated protein kinase activation facilitates AMPA receptor trafficking via the GDI·Rab5 complex: potential role in (S)-3,5-dihydroxyphenylglycineinduced long term depression,” The Journal of Biological Chemistry, vol. 279, no. 13, pp. 12286–12292, 2004. [24] J. G. Hanley, “AMPA receptor trafficking pathways and links to dendritic spine morphogenesis,” Cell Adhesion & Migration, vol. 2, no. 4, pp. 276–282, 2008. [25] J. Han, J. D. Lee, L. Bibbs, and R. J. Ulevitch, “A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells,” Science, vol. 265, no. 5173, pp. 808–811, 1994. [26] J. Rouse, P. Cohen, S. Trigon et al., “A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins,” Cell, vol. 78, no. 6, pp. 1027–1037, 1994. [27] N.W. Freshney, L. Rawlinson, F. Guesdon et al., “Interleukin- 1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27,” Cell, vol. 78, no. 6, pp. 1039– 1049, 1994. [28] Y. Shi and M. Gaestel, “In the cellular garden of forking paths: how p38 MAPKs signal for downstream assistance,” Biological Chemistry, vol. 383, no. 10, pp. 1519–1536, 2002. [29] M. Gaestel, “MAPKAP kinases—MKs—two’s company, three’s a crowd,” Nature Reviews Molecular Cell Biology, vol. 7, no. 2, pp. 120–130, 2006. [30] A. White, C. A. Pargellis, J. M. Studts, B. G. Werneburg, and B. T. Farmer, “Molecular basis of MAPK-activated protein kinase 2: p38 assembly,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 15, pp. 6353–6358, 2007. [31] L. J. Vician, G. Xu,W. Liu, J. D. Feldman, H. B.Machado, and H. R. Herschman, “MAPKAP kinase-2 is a primary response gene induced by depolarization in PC12 cells and in brain,” Journal of Neuroscience Research, vol. 78, no. 3, pp. 315–328, 2004. [32] D. Stokoe, K. Engel, D. G. Campbell, P. Cohen, and M. Gaestel, “Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian heat shock proteins,” FEBS Letters, vol. 313, no. 3, pp. 307–313, 1992. [33] L. New and J. Han, “The p38 MAP kinase pathway and its biological function,” Trends in Cardiovascular Medicine, vol. 8, no. 5, pp. 220–228, 1998. [34] S. Singh, D. W. Powell, M. J. Rane et al., “Identification of the p16-Arc subunit of the Arp 2/3 complex as a substrate of MAPK-activated protein kinase 2 by proteomic analysis,” The Journal of Biological Chemistry, vol. 278, no. 38, pp. 36410– 36417, 2003. [35] C. E. Eyers, H. McNeill, A. Knebel et al., “The phosphorylation of capz-interacting protein (capzip) by stress-activated protein kinases triggers its dissociation from capz,” Biochemical Journal, vol. 389, part 1, pp. 127–135, 2005. [36] C. K. Huang, L. Zhan, Y. Ai, and J. Jongstra, “Lsp1 is the major substrate for mitogen-activated protein kinase-activated protein kinase 2 in human neutrophils,” The Journal of Biological Chemistry, vol. 272, no. 1, pp. 17–19, 1997. [37] N. Ronkina,M.Menon, J. Schwermann et al., “Stress induced gene expression: a direct role for MAPKAP kinases in transcriptional activation of immediate early genes,” Nucleic Acids Research, vol. 39, no. 7, pp. 2503–2518, 2011. [38] S. A. Pintchovski, C. L. Peebles, H. J. Kim, E. Verdin, and S. Finkbeiner, “The serum response factor and a putative novel transcription factor regulate expression of the immediateearly gene Arc/Arg3.1 in neurons,” Journal of Neuroscience, vol. 29, no. 5, pp. 1525–1537, 2009. [39] C. R. Bramham, M. N. Alme, M. Bittins et al., “The Arc of synaptic memory,” Experimental Brain Research, vol. 200, no. 2, pp. 125–140, 2010. [40] C. L. Peebles, J. Yoo,M. T. Thwin, J. J. Palop, J. L. Noebels, and S. Finkbeiner, “Arc regulates spine morphology and maintains network stability in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 42, pp. 18173–18178, 2010. [41] S. Chowdhury, J. D. Shepherd, H. Okuno et al., “Arc/Arg3. 1 interacts with the endocytic machinery to regulate AMPA receptor trafficking,” Neuron, vol. 52, no. 3, pp. 445–459, 2006. [42] J. Wu, R. S. Petralia, H. Kurushima et al., “Arc/Arg3. 1 regulates an endosomal pathway essential for activity-dependent β-amyloid generation,” Cell, vol. 147, no. 3, pp. 615–628, 2011. [43] C. Ballatore, M. Y. L. Virginia, and J. Q. Trojanowski, “Taumediated neurodegeneration in Alzheimer’s disease and related disorders,” Nature Reviews Neuroscience, vol. 8, no. 9, pp. 663–672, 2007. [44] D. P. Hanger, B. H. Anderton, and W. Noble, “Tau phosphorylation: the therapeutic challenge for neurodegenerative disease,” Trends inMolecularMedicine, vol. 15, no. 3, pp. 112– 119, 2009. [45] B. R. Hoover, M. N. Reed, J. Su et al., “Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration,” Neuron, vol. 68, no. 6, pp. 1067–1081, 2010. [46] L. Martin, X. Latypova, and F. Terro, “Post-translational modifications of tau protein: implications for Alzheimer’s disease,”Neurochemistry International, vol. 58, no. 4, pp. 458– 471, 2011. [47] L. Bu´ee, T. Bussi`ere, V. Bu´ee-Scherrer, A. Delacourte, and P. R. Hof, “Tau protein isoforms, phosphorylation and role in neurodegenerative disorders,” Brain Research Reviews, vol. 33, no. 1, pp. 95–130, 2000. [48] L. I. Binder, A. Frankfurter, and L. I. Rebhun, “The distribution of tau in the mammalian central nervous system,” Journal of Cell Biology, vol. 101, no. 4, pp. 1371–1378, 1985. [49] C. Dotti, G. Banker, and L. Binder, “The expression and distribution of the microtubule-associated proteins tau and microtubule-associated protein 2 in hippocampal neurons in the rat in situ and in cell culture,” Neuroscience, vol. 23, no. 1, pp. 121–130, 1987. [50] J. W. Mandell and G. A. Banker, “A spatial gradient of tau protein phosphorylation in nascent axons,” Journal of Neuroscience, vol. 16, no. 18, pp. 5727–5740, 1996. [51] J. Avila, J. J. Lucas, M. P´erez, and F. Hern´andez, “Role of tau protein in both physiological and pathological conditions,” Physiological Reviews, vol. 84, no. 2, pp. 361–384, 2004. [52] S. C. Papasozomenos and L. I. Binder, “Phosphorylation determines two distinct species of tau in the central nervous system,” CellMotility and the Cytoskeleton, vol. 8, no. 3, pp. 210– 226, 1987. [53] C. A. Dickey, A. Kamal, K. Lundgren et al., “The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins,” The Journal of Clinical Investigation, vol. 117, no. 3, pp. 648–658, 2007. [54] A. Sengupta, J. Kabat, M. Novak, Q. Wu, I. Grundke-Iqbal, and K. Iqbal, “Phosphorylation of tau at both Thr 231 and Ser 262 is required for maximal inhibition of its binding to microtubules,” Archives of Biochemistry and Biophysics, vol. 357, no. 2, pp. 299–309, 1998. [55] W. J. Streit, R. E. Mrak, and W. S. T. Griffin, “Microglia and neuroinflammation: a pathological perspective,” Journal of Neuroinflammation, vol. 1, article 14, 2004. [56] C. Chao, S. Hu, and P. Peterson, “Glia, cytokines, and neurotoxicity,” Critical Reviews in Neurobiology, vol. 9, no. 2-3, pp. 189–205, 1995. [57] S. D. Skaper, “The brain as a target for inflammatory processes and neuroprotective strategies,” Annals of the New York Academy of Sciences, vol. 1122, no. 1, pp. 23–34, 2007. [58] S. J. Harper and P. Lograsso, “Signalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38,” Cellular Signalling, vol. 13, no. 5, pp. 299–310, 2001. [59] T.Obata, G. E. Brown, andM. B. Yaffe, “Map kinase pathways activated by stress: the p38 MAPK pathway,” Critical Care Medicine, vol. 28, no. 4, pp. 67–77, 2000. [60] A. Kotlyarov, A. Neininger, C. Schubert et al., “MAPKAP kinase 2 is essential for LPS-induced TNF-α biosynthesis,” Nature Cell Biology, vol. 1, no. 2, pp. 94–97, 1999. [61] N. Fyhrquist, S. Matikainen, and A. Lauerma, “MK2 signaling: lessons on tissue specificity in modulation of inflammation,” Journal of Investigative Dermatology, vol. 130, no. 2, pp. 342–344, 2010. [62] A. Neininger, D. Kontoyiannis, A. Kotlyarov et al., “MK2 targets AU-rich elements and regulates biosynthesis of tumor necrosis factor and interleukin-6 independently at different post-transcriptional levels,” The Journal of Biological Chemistry, vol. 277, no. 5, pp. 3065–3068, 2002. [63] A. A. Culbert, S. D. Skaper, D. R. Howlett et al., “MAPKactivated protein kinase 2 deficiency in microglia inhibits pro-inflammatory mediator release and resultant neurotoxicity: relevance to neuroinflammation in a transgenic mouse model of Alzheimer disease,” The Journal of Biological Chemistry, vol. 281, no. 33, pp. 23658–23667, 2006. [64] R. Brookmeyer, E. Johnson, K. Ziegler-Graham, and H. M. Arrighi, “Forecasting the global burden of Alzheimer’s disease,” Alzheimer’s and Dementia, vol. 3, no. 3, pp. 186–191, 2007. [65] S. T. DeKosky and S.W. Scheff, “Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity,” Annals of Neurology, vol. 27, no. 5, pp. 457–464, 1990. [66] M. Knobloch and I. M. Mansuy, “Dendritic spine loss and synaptic alterations in Alzheimer’s disease,”Molecular Neurobiology, vol. 37, no. 1, pp. 73–82, 2008. [67] I. Ferrer, F. Cruz-Sanchez, N. Guionnet, and T. Tunon, “A study of senile plaques with a combined method in brains of patients suffering from Alzheimer’s disease,” Archivos de Neurobiologia, vol. 53, no. 6, pp. 222–226, 1990. [68] P. Penzes and J. E. VanLeeuwen, “Impaired regulation of synaptic actin cytoskeleton in Alzheimer’s disease,” Brain Research Reviews, vol. 67, no. 1-2, pp. 184–192, 2011. [69] P. N. Lacor, M. C. Buniel, L. Chang et al., “Synaptic targeting by Alzheimer’s-related amyloid β oligomers,” Journal of Neuroscience, vol. 24, no. 45, pp. 10191–10200, 2004. [70] P. N. Lacor, M. C. Buniel, P. W. Furlow et al., “Aβ oligomerinduced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer’s disease,” Journal of Neuroscience, vol. 27, no. 4, pp. 796–807, 2007. [71] K. Hensley, R. A. Floyd, N. Y. Zheng et al., “P38 kinase is activated in the Alzheimer’s disease brain,” Journal of Neurochemistry, vol. 72, no. 5, pp. 2053–2058, 1999. [72] T. A. Fulga, I. Elson-Schwab, V. Khurana et al., “Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo,” Nature Cell Biology, vol. 9, no. 2, pp. 139–148, 2007. [73] D. M.Moraga, P. Nunez, J. Garrido, and R. B.Maccioni, “A τ fragment containing a repetitive sequence induces bundling of actin filaments,” Journal of Neurochemistry, vol. 61, no. 3, pp. 979–986, 1993. [74] P. K. Krishnamurthy and G. V.W. Johnson, “Mutant (r406w) human tau is hyperphosphorylated and does not efficiently bind microtubules in a neuronal cortical cell model,” The Journal of Biological Chemistry, vol. 279, no. 9, pp. 7893– 7900, 2004. [75] G. A. Farias, J. P. Munoz, J. Garrido, and R. B. Maccioni, “Tubulin, actin, and tau protein interactions and the study of their macromolecular assemblies,” Journal of Cellular Biochemistry, vol. 85, no. 2, pp. 315–324, 2002. [76] J. Z. Yu and M. M. Rasenick, “Tau associates with actin in differentiating PC12 cells,” FASEB Journal, vol. 20, no. 9, pp. 1452–1461, 2006. [77] H. He, X. Wang, R. Pan, D.Wang, M. Liu, and R. He, “The proline-rich domain of tau plays a role in interactions with actin,” BMC Cell Biology, vol. 10, no. 1, article 81, 2009. [78] P. Hotulainen and C. C. Hoogenraad, “Actin in dendritic spines: connecting dynamics to function,” Journal of Cell Biology, vol. 189, no. 4, pp. 619–629, 2010. [79] D. L. Rocca, S. Martin, E. L. Jenkins, and J. G. Hanley, “Inhibition of Arp2/3-mediated actin polymerization by PICK1 regulates neuronal morphology and AMPA receptor endocytosis,” Nature Cell Biology, vol. 10, no. 3, pp. 259–271, 2008. [80] Y. Nakamura, C. L. Wood, A. P. Patton et al., “PICK1 inhibition of the Arp2/3 complex controls dendritic spine size and synaptic plasticity,” EMBO Journal, vol. 30, no. 4, pp. 719–730, 2011. [81] H. Pyo, I. Jou, S. Jung, S. Hong, and E. Joe, “Mitogen-activated protein kinases activated by lipopolysaccharide and β- amyloid in cultured rat microglia,” Neuroreport, vol. 9, no. 5, pp. 871–874, 1998. [82] L. Munoz, H. Ranaivo, S. Roy et al., “A novel p38α MAPK inhibitor suppresses brain proinflammatory cytokine upregulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer’s diseasemouse model,” Journal of Neuroinflammation, vol. 4, no. 1, article 21, 2007. [83] S. H. Kim, C. J. Smith, and L. J. Van Eldik, “Importance of MAPK pathways for microglial pro-inflammatory cytokine IL-1β production,” Neurobiology of Aging, vol. 25, no. 4, pp. 431–439, 2004. [84] A. M. Bodles and S.W. Barger, “Secreted β-amyloid precursor protein activates microglia via JNK and p38-MAPK,” Neurobiology of Aging, vol. 26, no. 1, pp. 9–16, 2005. [85] D. T. Weldon, S. D. Rogers, J. R. Ghilardi et al., “Fibrillar β- amyloid induces microglial phagocytosis, expression of inducible nitric oxide synthase, and loss of a select population of neurons in the rat CNS in vivo,” Journal of Neuroscience, vol. 18, no. 6, pp. 2161–2173, 1998. [86] K. Shigematsu, P.McGeer, D.Walker, T. Ishii, and E.McGeer, “Reactive microglia/macrophages phagocytose amyloid precursor protein produced by neurons following neural damage,” Journal of Neuroscience Research, vol. 31, no. 3, pp. 443– 453, 1992. [87] M. G. Giovannini, C. Scali, C. Prosperi et al., “β-amyloidinduced inflammation and cholinergic hypofunction in the rat brain in vivo: involvement of the p38MAPK pathway,” Neurobiology of Disease, vol. 11, no. 2, pp. 257–274, 2002. [88] Y. Li, L. Liu, S.W. Barger, andW. S. T. Griffin, “Interleukin-1 mediates pathological effects of microglia on tau phosphorylation and on synaptophysin synthesis in cortical neurons through a p38-MAPK pathway,” Journal of Neuroscience, vol. 23, no. 5, pp. 1605–1611, 2003. [89] I. Ferrer, “Stress kinases involved in tau phosphorylation in Alzheimer’s disease, tauopathies and APP transgenic mice,” Neurotoxicity Research, vol. 6, no. 6, pp. 469–475, 2004. [90] M. J. Savage, Y. G. Lin, J. R. Ciallella, D. G. Flood, and R. W. Scott, “Activation of c-jun N-terminal kinase and p38 in an Alzheimer’s disease model is associated with amyloid deposition,” Journal of Neuroscience, vol. 22, no. 9, pp. 3376–3385, 2002. [91] X. Zhu, C. A. Rottkamp, A. Hartzler et al., “Activation of MKK6, an upstream activator of p38, in Alzheimer’s disease,” Journal of Neurochemistry, vol. 79, no. 2, pp. 311–318, 2001. [92] Y. Hashimoto, T. Niikura, T. Chiba et al., “The cytoplasmic domain of Alzheimer’s amyloid-β protein precursor causes sustained apoptosis signal-regulating kinase 1/c-Jun NH 2- terminal kinase-mediated neurotoxic signal via dimerization,” Journal of Pharmacology and Experimental Therapeutics, vol. 306, no. 3, pp. 889–902, 2003. [93] A. L. Peel, N. Sorscher, J. Y. Kim, V. Galvan, S. Chen, and D. E. Bredesen, “Tau phosphorylation in Alzheimer’s disease: potential involvement of an APP-MAP kinase complex,” Neuromolecular Medicine, vol. 5, no. 3, pp. 205–218, 2004. [94] G. T. Bramblett, M. Goedert, R. Jakes, S. E.Merrick, J. Q. Trojanowski, and V. M. Y. Lee, “Abnormal tau phosphorylation at Ser396 in Alzheimer’s disease recapitulates development and contributes to reduced microtubule binding,” Neuron, vol. 10, no. 6, pp. 1089–1099, 1993. [95] A.W.Hartzler, X. Zhu, S. L. Siedlak et al., “The p38 pathway is activated in pick disease and progressive supranuclear palsy: a mechanistic link between mitogenic pathways, oxidative stress, and tau,” Neurobiology of Aging, vol. 23, no. 5, pp. 855–859, 2002. [96] Parkinson’s UK, Number of people with Parkinson’s in the uk set to rise, 2012, http://www.parkinsons.org.uk/about us/ news/news items/all news/new parkinsons prevalence.aspx. [97] W. Poewe, “Non-motor symptoms in Parkinson’s disease,” European Journal of Neurology, vol. 15, no. 1, pp. 14–20, 2008. [98] S. Lesage and A. Brice, “Parkinson’s disease: from monogenic forms to genetic susceptibility factors,” Human Molecular Genetics, vol. 18, no. 1, pp. R48–R59, 2009. [99] M. R. Cookson, “α-synuclein and neuronal cell death,” Molecular Neurodegeneration, vol. 4, no. 1, article 9, 2009. [100] A. Klegeris, S. Pelech, B. I. Giasson et al., “α-synuclein activates stress signaling protein kinases in THP-1 cells and microglia,” Neurobiology of Aging, vol. 29, no. 5, pp. 739–752, 2008. [101] T. Thomas, M. Timmer, K. Cesnulevicius, E. Hitti, A. Kotlyarov, and M. Gaestel, “MAPKAP kinase 2-deficiency prevents neurons from cell death by reducing neuroinflammation— relevance in amouse model of Parkinson’s disease,” Journal of Neurochemistry, vol. 105, no. 5, pp. 2039–2052, 2008. |
| URI: | http://wrap.warwick.ac.uk/id/eprint/49225 |
Actions (login required)
![]() |
View Item |
Tools
Tools

