Compromised MAPK signaling in human diseases: an update

Archives of Toxicology

Volumn 89, Issue 6, 2015, Pages 867-882

  Kim, Eun Kyung ^a   Choi, Eui Ju ^a  

^a Korea University   (South Korea)

Author keywords

c Jun NH2 terminal kinase (JNK); Cancer; Extracellular signal regulated kinase (ERK); Mitogen activated protein kinase (MAPK); Neurodegenerative disease; p38 MAPK

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE KINASE;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; CELL PROLIFERATION; ENZYMOLOGY; HUMAN; IMMUNOLOGY; INNATE IMMUNITY; METABOLISM; NEOPLASM; OXIDATIVE STRESS; PARKINSON DISEASE; PATHOLOGY; SIGNAL TRANSDUCTION;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; CELL PROLIFERATION; HUMANS; IMMUNITY, INNATE; MAP KINASE SIGNALING SYSTEM; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; NEOPLASMS; OXIDATIVE STRESS; PARKINSON DISEASE;

EID: 84930672166     PISSN: 03405761     EISSN: 14320738     Source Type: Journal    
DOI: 10.1007/s00204-015-1472-2     Document Type: Review

References (166)

1. Ajroud-Driss S, Siddique T (2014) Sporadic and hereditary amyotrophic lateral sclerosis (ALS). Biochim Biophys Acta. doi:10.1016/j.bbadis.2014.08.010
2. Akundi RS, Huang Z, Eason J, Pandya JD, Zhi L, Cass WA, Sullivan PG, Bueler H (2011) Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice. PLoS ONE 6:e16038. doi:10.1371/journal.pone.0016038
3. Alami NH, Smith RB, Carrasco MA, Williams LA, Winborn CS, Han SS, Kiskinis E, Winborn B, Freibaum BD, Kanagaraj A, Clare AJ, Badders NM, Bilican B, Chaum E, Chandran S, Shaw CE, Eggan KC, Maniatis T, Taylor JP (2014) Axonal transport of TDP-43 mRNA granules is impaired by ALS-causing mutations. Neuron 81:536–543. doi:10.1016/j.neuron.2013.12.018
4. Al-Saif A, Al-Mohanna F, Bohlega S (2011) A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis. Ann Neurol 70:913–919. doi:10.1002/ana.22534
5. Ansieau S, Bastid J, Doreau A, Morel AP, Bouchet BP, Thomas C, Fauvet F, Puisieux I, Doglioni C, Piccinin S, Maestro R, Voeltzel T, Selmi A, Valsesia-Wittmann S, Caron de Fromentel C, Puisieux A (2008) Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. Cancer Cell 14:79–89. doi:10.1016/j.ccr.2008.06.005
6. Arthur JS, Ley SC (2013) Mitogen-activated protein kinases in innate immunity. Nat Rev Immunol 13:679–692. doi:10.1038/nri3495
7. Bach JP, Mengel D, Wahle T, Kautz A, Balzer-Geldsetzer M, Al-Abed Y, Dodel R, Bacher M (2011) The role of CNI-1493 in the function of primary microglia with respect to amyloid-beta. J Alzheimers Dis 26:69–80. doi:10.3233/JAD-2011-110179
8. Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, Molkentin JD (2005) Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434:658–662. doi:10.1038/nature03434
9. Banzhaf-Strathmann J, Benito E, May S, Arzberger T, Tahirovic S, Kretzschmar H, Fischer A, Edbauer D (2014) MicroRNA-125b induces tau hyperphosphorylation and cognitive deficits in Alzheimer’s disease. EMBO J 33:1667–1680. doi:10.15252/embj.201387576
10. Baralle M, Buratti E, Baralle FE (2013) The role of TDP-43 in the pathogenesis of ALS and FTLD. Biochem Soc Trans 41:1536–1540. doi:10.1042/BST20130186
11. Benilova I, De Strooper B (2011) An overlooked neurotoxic species in Alzheimer’s disease. Nat Neurosci 14:949–950. doi:10.1038/nn.2871
12. Benilova I, De Strooper B (2013) Neuroscience. Promiscuous Alzheimer’s amyloid: yet another partner. Science 341:1354–1355. doi:10.1126/science.1244166
13. Benilova I, Karran E, De Strooper B (2012) The toxic Abeta oligomer and Alzheimer’s disease: an emperor in need of clothes. Nat Neurosci 15:349–357. doi:10.1038/nn.3028
14. Blagden SP, Willis AE (2011) The biological and therapeutic relevance of mRNA translation in cancer. Nat Rev Clin Oncol 8:280–291. doi:10.1038/nrclinonc.2011.16
15. Bogaerts V, Nuytemans K, Reumers J, Pals P, Engelborghs S, Pickut B, Corsmit E, Peeters K, Schymkowitz J, De Deyn PP, Cras P, Rousseau F, Theuns J, Van Broeckhoven C (2008) Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson disease. Hum Mutat 29:832–840. doi:10.1002/humu.20713
16. Boussemart L, Malka-Mahieu H, Girault I, Allard D, Hemmingsson O, Tomasic G, Thomas M, Basmadjian C, Ribeiro N, Thuaud F, Mateus C, Routier E, Kamsu-Kom N, Agoussi S, Eggermont AM, Desaubry L, Robert C, Vagner S (2014) eIF4F is a nexus of resistance to anti-BRAF and anti-MEK cancer therapies. Nature 513:105–109. doi:10.1038/nature13572
17. Brennan DF, Dar AC, Hertz NT, Chao WC, Burlingame AL, Shokat KM, Barford D (2011) A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK. Nature 472:366–369. doi:10.1038/nature09860
18. Cameron B, Landreth GE (2010) Inflammation, microglia, and Alzheimer’s disease. Neurobiol Dis 37:503–509. doi:10.1016/j.nbd.2009.10.006
19. Cameron B, Tse W, Lamb R, Li X, Lamb BT, Landreth GE (2012) Loss of interleukin receptor-associated kinase 4 signaling suppresses amyloid pathology and alters microglial phenotype in a mouse model of Alzheimer’s disease. J Neurosci 32:15112–15123. doi:10.1523/JNEUROSCI.1729-12.2012
20. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2:401–404. doi:10.1158/2159-8290.CD-12-0095
21. Chaikuad A, Tacconi EM, Zimmer J, Liang Y, Gray NS, Tarsounas M, Knapp S (2014) A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics. Nat Chem Biol 10:853–860. doi:10.1038/nchembio.1629
22. Chen CY, Weng YH, Chien KY, Lin KJ, Yeh TH, Cheng YP, Lu CS, Wang HL (2012) (G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD. Cell Death Differ 19:1623–1633. doi:10.1038/cdd.2012.42
23. Chen D, Huang JF, Liu K, Zhang LQ, Yang Z, Chuai ZR, Wang YX, Shi DC, Huang Q, Fu WL (2014) BRAFV600E mutation and its association with clinicopathological features of colorectal cancer: a systematic review and meta-analysis. PLoS ONE 9:e90607. doi:10.1371/journal.pone.0090607
24. Cheung LW, Hennessy BT, Li J, Yu S, Myers AP, Djordjevic B, Lu Y, Stemke-Hale K, Dyer MD, Zhang F, Ju Z, Cantley LC, Scherer SE, Liang H, Lu KH, Broaddus RR, Mills GB (2011) High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stability. Cancer Discov 1:170–185. doi:10.1158/2159-8290.CD-11-0039
25. Cheung LW, Yu S, Zhang D, Li J, Ng PK, Panupinthu N, Mitra S, Ju Z, Yu Q, Liang H, Hawke DH, Lu Y, Broaddus RR, Mills GB (2014) Naturally occurring neomorphic PIK3R1 mutations activate the MAPK pathway, dictating therapeutic response to MAPK pathway inhibitors. Cancer Cell 26:479–494. doi:10.1016/j.ccell.2014.08.017
26. Chien WL, Lee TR, Hung SY, Kang KH, Wu RM, Lee MJ, Fu WM (2013) Increase of oxidative stress by a novel PINK1 mutation, P209A. Free Radic Biol Med 58:160–169. doi:10.1016/j.freeradbiomed.2012.12.008
27. Chiti F, Dobson CM (2006) Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem 75:333–366. doi:10.1146/annurev.biochem.75.101304.123901
28. Chlan-Fourney J, Zhao T, Walz W, Mousseau DD (2011) The increased density of p38 mitogen-activated protein kinase-immunoreactive microglia in the sensorimotor cortex of aged TgCRND8 mice is associated predominantly with smaller dense-core amyloid plaques. Eur J Neurosci 33:1433–1444. doi:10.1111/j.1460-9568.2010.07597.x
29. Choi WS, Abel G, Klintworth H, Flavell RA, Xia Z (2010) JNK3 mediates paraquat- and rotenone-induced dopaminergic neuron death. J Neuropathol Exp Neurol 69:511–520. doi:10.1097/NEN.0b013e3181db8100
30. Choi I, Kim J, Jeong HK, Kim B, Jou I, Park SM, Chen L, Kang UJ, Zhuang X, Joe EH (2013) PINK1 deficiency attenuates astrocyte proliferation through mitochondrial dysfunction, reduced AKT and increased p38 MAPK activation, and downregulation of EGFR. Glia 61:800–812. doi:10.1002/glia.22475
31. Cleary JD, Ranum LP (2014) Repeat associated non-ATG (RAN) translation: new starts in microsatellite expansion disorders. Curr Opin Genet Dev 26C:6–15. doi:10.1016/j.gde.2014.03.002
32. Crippa V, Sau D, Rusmini P, Boncoraglio A, Onesto E, Bolzoni E, Galbiati M, Fontana E, Marino M, Carra S, Bendotti C, De Biasi S, Poletti A (2010) The small heat shock protein B8 (HspB8) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS). Hum Mol Genet 19:3440–3456. doi:10.1093/hmg/ddq257
33. Das Thakur M, Stuart DD (2014) Molecular pathways: response and resistance to BRAF and MEK inhibitors in BRAF(V600E) tumors. Clin Cancer Res 20:1074–1080. doi:10.1158/1078-0432.CCR-13-0103
34. Das Thakur M, Salangsang F, Landman AS, Sellers WR, Pryer NK, Levesque MP, Dummer R, McMahon M, Stuart DD (2013) Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature 494:251–255. doi:10.1038/nature11814
35. Davis RJ (2000) Signal transduction by the JNK group of MAP kinases. Cell 103:239–252
36. Dawson TM, Dawson VL (2014) Parkin plays a role in sporadic Parkinson’s disease. Neurodegener Dis 13:69–71. doi:10.1159/000354307
37. Defea K (2008) Beta-arrestins and heterotrimeric G-proteins: collaborators and competitors in signal transduction. Br J Pharmacol 153(Suppl 1):S298–S309. doi:10.1038/sj.bjp.0707508
38. Desideri E, Martins LM (2012) Mitochondrial stress signalling: HTRA2 and Parkinson’s disease. Int J Cell Biol 2012:607929. doi:10.1155/2012/607929
39. Diaz-Flores E, Goldschmidt H, Depeille P, Ng V, Akutagawa J, Krisman K, Crone M, Burgess MR, Williams O, Houseman B, Shokat K, Sampath D, Bollag G, Roose JP, Braun BS, Shannon K (2013) PLC-gamma and PI3K link cytokines to ERK activation in hematopoietic cells with normal and oncogenic Kras. Sci Signal 6:ra105. doi:10.1126/scisignal.2004125
40. Dillon LM, Bean JR, Yang W, Shee K, Symonds LK, Balko JM, McDonald WH, Liu S, Gonzalez-Angulo AM, Mills GB, Arteaga CL, Miller TW (2014) P-REX1 creates a positive feedback loop to activate growth factor receptor, PI3 K/AKT and MEK/ERK signaling in breast cancer. Oncogene. doi:10.1038/onc.2014.328
41. Dinarello CA (2010) Anti-inflammatory agents: present and future. Cell 140:935–950. doi:10.1016/j.cell.2010.02.043
42. Dougherty MK, Ritt DA, Zhou M, Specht SI, Monson DM, Veenstra TD, Morrison DK (2009) KSR2 is a calcineurin substrate that promotes ERK cascade activation in response to calcium signals. Mol Cell 34:652–662. doi:10.1016/j.molcel.2009.06.001
43. Drosten M, Sum EY, Lechuga CG, Simon-Carrasco L, Jacob HK, Garcia-Medina R, Huang S, Beijersbergen RL, Bernards R, Barbacid M (2014) Loss of p53 induces cell proliferation via Ras-independent activation of the Raf/Mek/Erk signaling pathway. Proc Natl Acad Sci USA 111:15155–15160. doi:10.1073/pnas.1417549111
44. Du H, Guo L, Fang F, Chen D, Sosunov AA, McKhann GM, Yan Y, Wang C, Zhang H, Molkentin JD, Gunn-Moore FJ, Vonsattel JP, Arancio O, Chen JX, Yan SD (2008) Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer’s disease. Nat Med 14:1097–1105. doi:10.1038/nm.1868
45. Du H, Guo L, Yan SS (2012) Synaptic mitochondrial pathology in Alzheimer’s disease. Antioxid Redox Signal 16:1467–1475. doi:10.1089/ars.2011.4277
46. Dzamko N, Zhou J, Huang Y, Halliday GM (2014) Parkinson’s disease-implicated kinases in the brain; insights into disease pathogenesis. Front Mol Neurosci 7:57. doi:10.3389/fnmol.2014.00057
47. El Khoury J, Hickman SE, Thomas CA, Cao L, Silverstein SC, Loike JD (1996) Scavenger receptor-mediated adhesion of microglia to beta-amyloid fibrils. Nature 382:716–719. doi:10.1038/382716a0
48. Feng Y, Chambers JW, Iqbal S, Koenig M, Park H, Cherry L, Hernandez P, Figuera-Losada M, LoGrasso PV (2013) A small molecule bidentate-binding dual inhibitor probe of the LRRK2 and JNK kinases. ACS Chem Biol 8:1747–1754. doi:10.1021/cb3006165
49. Fiesel FC, Kahle PJ (2011) TDP-43 and FUS/TLS: cellular functions and implications for neurodegeneration. FEBS J 278:3550–3568. doi:10.1111/j.1742-4658.2011.08258.x
50. Fitzgerald JC, Camprubi MD, Dunn L, Wu HC, Ip NY, Kruger R, Martins LM, Wood NW, Plun-Favreau H (2012) Phosphorylation of HtrA2 by cyclin-dependent kinase-5 is important for mitochondrial function. Cell Death Differ 19:257–266. doi:10.1038/cdd.2011.90
51. Fuchs A, Kutterer S, Muhling T, Duda J, Schutz B, Liss B, Keller BU, Roeper J (2013) Selective mitochondrial Ca2+ uptake deficit in disease endstage vulnerable motoneurons of the SOD1G93A mouse model of amyotrophic lateral sclerosis. J Physiol 591:2723–2745. doi:10.1113/jphysiol.2012.247981
52. Gan X, Huang S, Wu L, Wang Y, Hu G, Li G, Zhang H, Yu H, Swerdlow RH, Chen JX, Yan SS (2014) Inhibition of ERK-DLP1 signaling and mitochondrial division alleviates mitochondrial dysfunction in Alzheimer’s disease cybrid cell. Biochim Biophys Acta 1842:220–231. doi:10.1016/j.bbadis.2013.11.009
53. Gandhi S, Wood NW (2005) Molecular pathogenesis of Parkinson’s disease. Hum Mol Genet 14:2749–2755. doi:10.1093/hmg/ddi308
54. Gandy S, DeKosky ST (2013) Toward the treatment and prevention of Alzheimer’s disease: rational strategies and recent progress. Annu Rev Med 64:367–383. doi:10.1146/annurev-med-092611-084441
55. Gao F, Chen D, Hu Q, Wang G (2013) Rotenone directly induces BV2 cell activation via the p38 MAPK pathway. PLoS ONE 8:e72046. doi:10.1371/journal.pone.0072046
56. Gautier CA, Corti O, Brice A (2014) Mitochondrial dysfunctions in Parkinson’s disease. Rev Neurol (Paris) 170:339–343. doi:10.1016/j.neurol.2013.06.003
57. Ghavami S, Shojaei S, Yeganeh B, Ande SR, Jangamreddy JR, Mehrpour M, Christoffersson J, Chaabane W, Moghadam AR, Kashani HH, Hashemi M, Owji AA, Los MJ (2014) Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog Neurobiol 112:24–49. doi:10.1016/j.pneurobio.2013.10.004
58. Giacobini E, Becker RE (2007) One hundred years after the discovery of Alzheimer’s disease. A turning point for therapy? J Alzheimers Dis 12:37–52
59. Giraldo E, Lloret A, Fuchsberger T, Vina J (2014) Abeta and tau toxicities in Alzheimer’s are linked via oxidative stress-induced p38 activation: protective role of vitamin E. Redox Biol 2:873–877. doi:10.1016/j.redox.2014.03.002
60. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140:918–934. doi:10.1016/j.cell.2010.02.016
61. Goedert M (2001) Alpha-synuclein and neurodegenerative diseases. Nat Rev Neurosci 2:492–501. doi:10.1038/35081564
62. Grossi V, Peserico A, Tezil T, Simone C (2014) p38alpha MAPK pathway: a key factor in colorectal cancer therapy and chemoresistance. World J Gastroenterol 20:9744–9758. doi:10.3748/wjg.v20.i29.9744
63. Hayashi T, Su TP (2007) Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival. Cell 131:596–610. doi:10.1016/j.cell.2007.08.036
64. He C, Levine B (2010) The Beclin 1 interactome. Curr Opin Cell Biol 22:140–149. doi:10.1016/j.ceb.2010.01.001
65. Huang S, Holzel M, Knijnenburg T, Schlicker A, Roepman P, McDermott U, Garnett M, Grernrum W, Sun C, Prahallad A, Groenendijk FH, Mittempergher L, Nijkamp W, Neefjes J, Salazar R, Ten Dijke P, Uramoto H, Tanaka F, Beijersbergen RL, Wessels LF, Bernards R (2012) MED12 controls the response to multiple cancer drugs through regulation of TGF-beta receptor signaling. Cell 151:937–950. doi:10.1016/j.cell.2012.10.035
66. Hwang S, Kim D, Choi G, An SW, Hong YK, Suh YS, Lee MJ, Cho KS (2010) Parkin suppresses c-Jun N-terminal kinase-induced cell death via transcriptional regulation in Drosophila. Mol Cells 29:575–580. doi:10.1007/s10059-010-0068-1
67. Hwang S, Song S, Hong YK, Choi G, Suh YS, Han SY, Lee M, Park SH, Lee JH, Lee S, Bang SM, Jeong Y, Chung WJ, Lee IS, Jeong G, Chung J, Cho KS (2013) Drosophila DJ-1 decreases neural sensitivity to stress by negatively regulating Daxx-like protein through dFOXO. PLoS Genet 9:e1003412. doi:10.1371/journal.pgen.1003412
68. Hyttinen JM, Niittykoski M, Salminen A, Kaarniranta K (2013) Maturation of autophagosomes and endosomes: a key role for Rab7. Biochim Biophys Acta 1833:503–510. doi:10.1016/j.bbamcr.2012.11.018
69. Hyttinen JM, Amadio M, Viiri J, Pascale A, Salminen A, Kaarniranta K (2014) Clearance of misfolded and aggregated proteins by aggrephagy and implications for aggregation diseases. Ageing Res Rev 18C:16–28. doi:10.1016/j.arr.2014.07.002
70. Jaeger PA, Pickford F, Sun CH, Lucin KM, Masliah E, Wyss-Coray T (2010) Regulation of amyloid precursor protein processing by the Beclin 1 complex. PLoS ONE 5:e11102. doi:10.1371/journal.pone.0011102
71. Jakob-Roetne R, Jacobsen H (2009) Alzheimer’s disease: from pathology to therapeutic approaches. Angew Chem Int Ed Engl 48:3030–3059. doi:10.1002/anie.200802808
72. Jessen WJ, Miller SJ, Jousma E, Wu J, Rizvi TA, Brundage ME, Eaves D, Widemann B, Kim MO, Dombi E, Sabo J, Hardiman Dudley A, Niwa-Kawakita M, Page GP, Giovannini M, Aronow BJ, Cripe TP, Ratner N (2013) MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors. J Clin Invest 123:340–347. doi:10.1172/JCI60578
73. Kaul T, Credle J, Haggerty T, Oaks AW, Masliah E, Sidhu A (2011) Region-specific tauopathy and synucleinopathy in brain of the alpha-synuclein overexpressing mouse model of Parkinson’s disease. BMC Neurosci 12:79. doi:10.1186/1471-2202-12-79
74. Kelkar N, Standen CL, Davis RJ (2005) Role of the JIP4 scaffold protein in the regulation of mitogen-activated protein kinase signaling pathways. Mol Cell Biol 25:2733–2743. doi:10.1128/MCB.25.7.2733-2743.2005
75. Kim EK, Choi EJ (2010) Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta 1802:396–405. doi:10.1016/j.bbadis.2009.12.009
76. Kim SJ, Park YJ, Hwang IY, Youdim MB, Park KS, Oh YJ (2012) Nuclear translocation of DJ-1 during oxidative stress-induced neuronal cell death. Free Radic Biol Med 53:936–950. doi:10.1016/j.freeradbiomed.2012.05.035
77. Kim J, Kim TY, Cho KS, Kim HN, Koh JY (2013a) Autophagy activation and neuroprotection by progesterone in the G93A-SOD1 transgenic mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 59:80–85. doi:10.1016/j.nbd.2013.07.011
78. 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 anti-inflammatory function of DJ-1. Neurobiol Dis 60:1–10. doi:10.1016/j.nbd.2013.08.007
79. Kitazawa M, Cheng D, Tsukamoto MR, Koike MA, Wes PD, Vasilevko V, Cribbs DH, LaFerla FM (2011) Blocking IL-1 signaling rescues cognition, attenuates tau pathology, and restores neuronal beta-catenin pathway function in an Alzheimer’s disease model. J Immunol 187:6539–6549. doi:10.4049/jimmunol.1100620
80. Kuperstein I, Broersen K, Benilova I, Rozenski J, Jonckheere W, Debulpaep M, Vandersteen A, Segers-Nolten I, Van Der Werf K, Subramaniam V, Braeken D, Callewaert G, Bartic C, D’Hooge R, Martins IC, Rousseau F, Schymkowitz J, De Strooper B (2010) Neurotoxicity of Alzheimer’s disease Abeta peptides is induced by small changes in the Abeta42 to Abeta40 ratio. EMBO J 29:3408–3420. doi:10.1038/emboj.2010.211
81. Le LQ, Parada LF (2007) Tumor microenvironment and neurofibromatosis type I: connecting the GAPs. Oncogene 26:4609–4616. doi:10.1038/sj.onc.1210261
82. Le WD, Xu P, Jankovic J, Jiang H, Appel SH, Smith RG, Vassilatis DK (2003) Mutations in NR4A2 associated with familial Parkinson disease. Nat Genet 33:85–89. doi:10.1038/ng1066
83. Lee HJ, Patel S, Lee SJ (2005) Intravesicular localization and exocytosis of alpha-synuclein and its aggregates. J Neurosci 25:6016–6024. doi:10.1523/JNEUROSCI.0692-05.2005
84. Lee JK, Shin JH, Hwang SG, Gwag BJ, McKee AC, Lee J, Kowall NW, Ryu H, Lim DS, Choi EJ (2013a) MST1 functions as a key modulator of neurodegeneration in a mouse model of ALS. Proc Natl Acad Sci USA 110:12066–12071. doi:10.1073/pnas.1300894110
85. Lee M, McGeer E, Kodela R, Kashfi K, McGeer PL (2013b) NOSH-aspirin (NBS-1120), a novel nitric oxide and hydrogen sulfide releasing hybrid, attenuates neuroinflammation induced by microglial and astrocytic activation: a new candidate for treatment of neurodegenerative disorders. Glia 61:1724–1734. doi:10.1002/glia.22553
86. Lim E, Lee S, Li E, Kim Y, Park S (2011a) Ghrelin protects spinal cord motoneurons against chronic glutamate-induced excitotoxicity via ERK1/2 and phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-3beta pathways. Exp Neurol 230:114–122. doi:10.1016/j.expneurol.2011.04.003
87. Lim JE, Kou J, Song M, Pattanayak A, Jin J, Lalonde R, Fukuchi K (2011b) MyD88 deficiency ameliorates beta-amyloidosis in an animal model of Alzheimer’s disease. Am J Pathol 179:1095–1103. doi:10.1016/j.ajpath.2011.05.045
88. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795. doi:10.1038/nature05292
89. Maezawa I, Zimin PI, Wulff H, Jin LW (2011) Amyloid-beta protein oligomer at low nanomolar concentrations activates microglia and induces microglial neurotoxicity. J Biol Chem 286:3693–3706. doi:10.1074/jbc.M110.135244
90. Mendez EF, Sattler R (2014) Biomarker development for C9orf72 repeat expansion in ALS. Brain Res. doi:10.1016/j.brainres.2014.09.041
91. Menzies FM, Yenisetti SC, Min KT (2005) Roles of drosophila DJ-1 in survival of dopaminergic neurons and oxidative stress. Curr Biol 15:1578–1582. doi:10.1016/j.cub.2005.07.036
92. Mizielinska S, Isaacs AM (2014) C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia: gain or loss of function? Curr Opin Neurol 27:515–523. doi:10.1097/WCO.0000000000000130
93. Mizielinska S, Gronke S, Niccoli T, Ridler CE, Clayton EL, Devoy A, Moens T, Norona FE, Woollacott IO, Pietrzyk J, Cleverley K, Nicoll AJ, Pickering-Brown S, Dols J, Cabecinha M, Hendrich O, Fratta P, Fisher EM, Partridge L, Isaacs AM (2014) C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins. Science 345:1192–1194. doi:10.1126/science.1256800
94. Morfini GA, Bosco DA, Brown H, Gatto R, Kaminska A, Song Y, Molla L, Baker L, Marangoni MN, Berth S, Tavassoli E, Bagnato C, Tiwari A, Hayward LJ, Pigino GF, Watterson DM, Huang CF, Banker G, Brown RH Jr, Brady ST (2013) Inhibition of fast axonal transport by pathogenic SOD1 involves activation of p38 MAP kinase. PLoS ONE 8:e65235. doi:10.1371/journal.pone.0065235
95. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–133. doi:10.1126/science.1134108
96. Neuzillet C, Tijeras-Raballand A, de Mestier L, Cros J, Faivre S, Raymond E (2014) MEK in cancer and cancer therapy. Pharmacol Ther 141:160–171. doi:10.1016/j.pharmthera.2013.10.001
97. Newlaczyl AU, Hood FE, Coulson JM, Prior IA (2014) Decoding RAS isoform and codon-specific signalling. Biochem Soc Trans 42:742–746. doi:10.1042/BST20140057
98. Ni Y, Zhao X, Bao G, Zou L, Teng L, Wang Z, Song M, Xiong J, Bai Y, Pei G (2006) Activation of beta2-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation. Nat Med 12:1390–1396. doi:10.1038/nm1485
99. Nikolaev SI, Rimoldi D, Iseli C, Valsesia A, Robyr D, Gehrig C, Harshman K, Guipponi M, Bukach O, Zoete V, Michielin O, Muehlethaler K, Speiser D, Beckmann JS, Xenarios I, Halazonetis TD, Jongeneel CV, Stevenson BJ, Antonarakis SE (2012) Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma. Nat Genet 44:133–139. doi:10.1038/ng.1026
100. Nithianandarajah-Jones GN, Wilm B, Goldring CE, Muller J, Cross MJ (2012) ERK5: structure, regulation and function. Cell Signal 24:2187–2196. doi:10.1016/j.cellsig.2012.07.007
101. Nixon RA (2013) The role of autophagy in neurodegenerative disease. Nat Med 19:983–997. doi:10.1038/nm.3232
102. Nixon RA, Yang DS (2011) Autophagy failure in Alzheimer’s disease–locating the primary defect. Neurobiol Dis 43:38–45. doi:10.1016/j.nbd.2011.01.021
103. O’Callaghan C, Fanning LJ, Barry OP (2014) p38delta MAPK: emerging roles of a neglected isoform. Int J Cell Biol 2014:272689. doi:10.1155/2014/272689
104. Ono Y, Tanaka H, Takata M, Nagahara Y, Noda Y, Tsuruma K, Shimazawa M, Hozumi I, Hara H (2014) SA4503, a sigma-1 receptor agonist, suppresses motor neuron damage in in vitro and in vivo amyotrophic lateral sclerosis models. Neurosci Lett 559:174–178. doi:10.1016/j.neulet.2013.12.005
105. Pan CQ, Sudol M, Sheetz M, Low BC (2012) Modularity and functional plasticity of scaffold proteins as p(l)acemakers in cell signaling. Cell Signal 24:2143–2165. doi:10.1016/j.cellsig.2012.06.002
106. Park HS, Cho SG, Kim CK, Hwang HS, Noh KT, Kim MS, Huh SH, Kim MJ, Ryoo K, Kim EK, Kang WJ, Lee JS, Seo JS, Ko YG, Kim S, Choi EJ (2002) Heat shock protein hsp72 is a negative regulator of apoptosis signal-regulating kinase 1. Mol Cell Biol 22:7721–7730
107. Paul P, de Belleroche J (2014) The role of d-serine and glycine as co-agonists of NMDA receptors in motor neuron degeneration and amyotrophic lateral sclerosis (ALS). Front Synaptic Neurosci 6:10. doi:10.3389/fnsyn.2014.00010
108. Peeper DS, Upton TM, Ladha MH, Neuman E, Zalvide J, Bernards R, DeCaprio JA, Ewen ME (1997) Ras signalling linked to the cell-cycle machinery by the retinoblastoma protein. Nature 386:177–181. doi:10.1038/386177a0
109. Perlson E, Jeong GB, Ross JL, Dixit R, Wallace KE, Kalb RG, Holzbaur EL (2009) A switch in retrograde signaling from survival to stress in rapid-onset neurodegeneration. J Neurosci 29:9903–9917. doi:10.1523/JNEUROSCI.0813-09.2009
110. Peti W, Page R (2013) Molecular basis of MAP kinase regulation. Protein Sci 22:1698–1710. doi:10.1002/pro.2374
111. Peviani M, Salvaneschi E, Bontempi L, Petese A, Manzo A, Rossi D, Salmona M, Collina S, Bigini P, Curti D (2014) Neuroprotective effects of the Sigma-1 receptor (S1R) agonist PRE-084, in a mouse model of motor neuron disease not linked to SOD1 mutation. Neurobiol Dis 62:218–232. doi:10.1016/j.nbd.2013.10.010
112. Pickford F, Masliah E, Britschgi M, Lucin K, Narasimhan R, Jaeger PA, Small S, Spencer B, Rockenstein E, Levine B, Wyss-Coray T (2008) The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J Clin Invest 118:2190–2199. doi:10.1172/JCI33585
113. Pratico D (2008) Oxidative stress hypothesis in Alzheimer’s disease: a reappraisal. Trends Pharmacol Sci 29:609–615. doi:10.1016/j.tips.2008.09.001
114. Rainey-Smith SR, Andersson DA, Williams RJ, Rattray M (2010) Tumour necrosis factor alpha induces rapid reduction in AMPA receptor-mediated calcium entry in motor neurons by increasing cell surface expression of the GluR2 subunit: relevance to neurodegeneration. J Neurochem 113:692–703. doi:10.1111/j.1471-4159.2010.06634.x
115. Rauen KA (2013) The RASopathies. Annu Rev Genomics Hum Genet 14:355–369. doi:10.1146/annurev-genom-091212-153523
116. Ravits JM, La Spada AR (2009) ALS motor phenotype heterogeneity, focality, and spread: deconstructing motor neuron degeneration. Neurology 73:805–811. doi:10.1212/WNL.0b013e3181b6bbbd
117. Reed-Geaghan EG, Savage JC, Hise AG, Landreth GE (2009) CD14 and toll-like receptors 2 and 4 are required for fibrillar A{beta}-stimulated microglial activation. J Neurosci 29:11982–11992. doi:10.1523/JNEUROSCI.3158-09.2009
118. Reinhardt P, Schmid B, Burbulla LF, Schondorf DC, Wagner L, Glatza M, Hoing S, Hargus G, Heck SA, Dhingra A, Wu G, Muller S, Brockmann K, Kluba T, Maisel M, Kruger R, Berg D, Tsytsyura Y, Thiel CS, Psathaki OE, Klingauf J, Kuhlmann T, Klewin M, Muller H, Gasser T, Scholer HR, Sterneckert J (2013) Genetic correction of a LRRK2 mutation in human iPSCs links parkinsonian neurodegeneration to ERK-dependent changes in gene expression. Cell Stem Cell 12:354–367. doi:10.1016/j.stem.2013.01.008
119. Roberts AE, Allanson JE, Tartaglia M, Gelb BD (2013) Noonan syndrome. Lancet 381:333–342. doi:10.1016/S0140-6736(12)61023-X
120. Roodveldt C, Labrador-Garrido A, Gonzalez-Rey E, Fernandez-Montesinos R, Caro M, Lachaud CC, Waudby CA, Delgado M, Dobson CM, Pozo D (2010) Glial innate immunity generated by non-aggregated alpha-synuclein in mouse: differences between wild-type and Parkinson’s disease-linked mutants. PLoS ONE 5:e13481. doi:10.1371/journal.pone.0013481
121. Rovida E, Di Maira G, Tusa I, Cannito S, Paternostro C, Navari N, Vivoli E, Deng X, Gray NS, Esparis-Ogando A, David E, Pandiella A, Dello Sbarba P, Parola M, Marra F (2014) The mitogen-activated protein kinase ERK5 regulates the development and growth of hepatocellular carcinoma. Gut. doi:10.1136/gutjnl-2014-306761
122. Rowland LP, Shneider NA (2001) Amyotrophic lateral sclerosis. N Engl J Med 344:1688–1700. doi:10.1056/NEJM200105313442207
123. Rudalska R, Dauch D, Longerich T, McJunkin K, Wuestefeld T, Kang TW, Hohmeyer A, Pesic M, Leibold J, von Thun A, Schirmacher P, Zuber J, Weiss KH, Powers S, Malek NP, Eilers M, Sipos B, Lowe SW, Geffers R, Laufer S, Zender L (2014) In vivo RNAi screening identifies a mechanism of sorafenib resistance in liver cancer. Nat Med 20:1138–1146. doi:10.1038/nm.3679
124. Sabio G, Davis RJ (2014) TNF and MAP kinase signalling pathways. Semin Immunol 26:237–245. doi:10.1016/j.smim.2014.02.009
125. Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, Gage FH, Glass CK (2009) A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 137:47–59. doi:10.1016/j.cell.2009.01.038
126. Saito T, Suemoto T, Brouwers N, Sleegers K, Funamoto S, Mihira N, Matsuba Y, Yamada K, Nilsson P, Takano J, Nishimura M, Iwata N, Van Broeckhoven C, Ihara Y, Saido TC (2011) Potent amyloidogenicity and pathogenicity of Abeta43. Nat Neurosci 14:1023–1032. doi:10.1038/nn.2858
127. Sale MJ, Cook SJ (2014) Intrinsic and acquired resistance to MEK1/2 inhibitors in cancer. Biochem Soc Trans 42:776–783. doi:10.1042/BST20140129
128. Salminen A, Kaarniranta K, Kauppinen A, Ojala J, Haapasalo A, Soininen H, Hiltunen M (2013) Impaired autophagy and APP processing in Alzheimer’s disease: the potential role of Beclin 1 interactome. Prog Neurobiol 106–107:33–54. doi:10.1016/j.pneurobio.2013.06.002
129. Sama RR, Ward CL, Bosco DA (2014) Functions of FUS/TLS from DNA repair to stress response: implications for ALS. ASN Neuro 6. doi:10.1177/1759091414544472
130. Sarkar S, Rubinsztein DC (2008) Small molecule enhancers of autophagy for neurodegenerative diseases. Mol BioSyst 4:895–901. doi:10.1039/b804606a
131. Sasabe J, Chiba T, Yamada M, Okamoto K, Nishimoto I, Matsuoka M, Aiso S (2007) D-serine is a key determinant of glutamate toxicity in amyotrophic lateral sclerosis. EMBO J 26:4149–4159. doi:10.1038/sj.emboj.7601840
132. Scarffe LA, Stevens DA, Dawson VL, Dawson TM (2014) Parkin and PINK1: much more than mitophagy. Trends Neurosci 37:315–324. doi:10.1016/j.tins.2014.03.004
133. Schapansky J, Nardozzi JD, LaVoie MJ (2014) The complex relationships between microglia, alpha-synuclein, and LRRK2 in Parkinson’s disease. Neuroscience. doi:10.1016/j.neuroscience.2014.09.049
134. Sclip A, Tozzi A, Abaza A, Cardinetti D, Colombo I, Calabresi P, Salmona M, Welker E, Borsello T (2014) c-Jun N-terminal kinase has a key role in Alzheimer disease synaptic dysfunction in vivo. Cell Death Dis 5:e1019. doi:10.1038/cddis.2013.559
135. Seki E, Brenner DA, Karin M (2012) A liver full of JNK: signaling in regulation of cell function and disease pathogenesis, and clinical approaches. Gastroenterology 143:307–320. doi:10.1053/j.gastro.2012.06.004
136. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM, Walsh DM, Sabatini BL, Selkoe DJ (2008) Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 14:837–842. doi:10.1038/nm1782
137. Sharma C, Vomastek T, Tarcsafalvi A, Catling AD, Schaeffer HJ, Eblen ST, Weber MJ (2005) MEK partner 1 (MP1): regulation of oligomerization in MAP kinase signaling. J Cell Biochem 94:708–719. doi:10.1002/jcb.20344
138. Song Y, Nagy M, Ni W, Tyagi NK, Fenton WA, Lopez-Giraldez F, Overton JD, Horwich AL, Brady ST (2013) Molecular chaperone Hsp110 rescues a vesicle transport defect produced by an ALS-associated mutant SOD1 protein in squid axoplasm. Proc Natl Acad Sci USA 110:5428–5433. doi:10.1073/pnas.1303279110
139. Stoica R, De Vos KJ, Paillusson S, Mueller S, Sancho RM, Lau KF, Vizcay-Barrena G, Lin WL, Xu YF, Lewis J, Dickson DW, Petrucelli L, Mitchell JC, Shaw CE, Miller CC (2014) ER-mitochondria associations are regulated by the VAPB-PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43. Nat Commun 5:3996. doi:10.1038/ncomms4996
140. Su Z, Zhang Y, Gendron TF, Bauer PO, Chew J, Yang WY, Fostvedt E, Jansen-West K, Belzil VV, Desaro P, Johnston A, Overstreet K, Oh SY, Todd PK, Berry JD, Cudkowicz ME, Boeve BF, Dickson D, Floeter MK, Traynor BJ, Morelli C, Ratti A, Silani V, Rademakers R, Brown RH, Rothstein JD, Boylan KB, Petrucelli L, Disney MD (2014) Discovery of a biomarker and lead small molecules to target r(GGGGCC)-associated defects in c9FTD/ALS. Neuron 83:1043–1050. doi:10.1016/j.neuron.2014.07.041
141. Sugiura A, McLelland GL, Fon EA, McBride HM (2014) A new pathway for mitochondrial quality control: mitochondrial-derived vesicles. EMBO J. doi:10.15252/embj.201488104
142. Sul JW, Park MY, Shin J, Kim YR, Yoo SE, Kong YY, Kwon KS, Lee YH, Kim E (2013) Accumulation of the parkin substrate, FAF1, plays a key role in the dopaminergic neurodegeneration. Hum Mol Genet 22:1558–1573. doi:10.1093/hmg/ddt006
143. Swinnen B, Robberecht W (2014) The phenotypic variability of amyotrophic lateral sclerosis. Nat Rev Neurol 10:661–670. doi:10.1038/nrneurol.2014.184
144. Tadic V, Prell T, Lautenschlaeger J, Grosskreutz J (2014) The ER mitochondria calcium cycle and ER stress response as therapeutic targets in amyotrophic lateral sclerosis. Front Cell Neurosci 8:147. doi:10.3389/fncel.2014.00147
145. Tain LS, Chowdhury RB, Tao RN, Plun-Favreau H, Moisoi N, Martins LM, Downward J, Whitworth AJ, Tapon N (2009) Drosophila HtrA2 is dispensable for apoptosis but acts downstream of PINK1 independently from Parkin. Cell Death Differ 16:1118–1125. doi:10.1038/cdd.2009.23
146. Takeda K, Naguro I, Nishitoh H, Matsuzawa A, Ichijo H (2011) Apoptosis signaling kinases: from stress response to health outcomes. Antioxid Redox Signal 15:719–761. doi:10.1089/ars.2010.3392
147. Tan JL, Li QX, Ciccotosto GD, Crouch PJ, Culvenor JG, White AR, Evin G (2013) Mild oxidative stress induces redistribution of BACE1 in non-apoptotic conditions and promotes the amyloidogenic processing of Alzheimer’s disease amyloid precursor protein. PLoS ONE 8:e61246. doi:10.1371/journal.pone.0061246
148. Tan W, Pasinelli P, Trotti D (2014) Role of mitochondria in mutant SOD1 linked amyotrophic lateral sclerosis. Biochim Biophys Acta 1842:1295–1301. doi:10.1016/j.bbadis.2014.02.009
149. Tapia-Gonzalez S, Giraldez-Perez RM, Cuartero MI, Casarejos MJ, Mena MA, Wang XF, Sanchez-Capelo A (2011) Dopamine and alpha-synuclein dysfunction in Smad3 null mice. Mol Neurodegener 6:72. doi:10.1186/1750-1326-6-72
150. Tobon-Velasco JC, Limon-Pacheco JH, Orozco-Ibarra M, Macias-Silva M, Vazquez-Victorio G, Cuevas E, Ali SF, Cuadrado A, Pedraza-Chaverri J, Santamaria A (2013) 6-OHDA-induced apoptosis and mitochondrial dysfunction are mediated by early modulation of intracellular signals and interaction of Nrf2 and NF-kappaB factors. Toxicology 304:109–119. doi:10.1016/j.tox.2012.12.011
151. Torii S, Yamamoto T, Tsuchiya Y, Nishida E (2006) ERK MAP kinase in G cell cycle progression and cancer. Cancer Sci 97:697–702. doi:10.1111/j.1349-7006.2006.00244.x
152. Tovar YRLB, Tapia R (2010) VEGF protects spinal motor neurons against chronic excitotoxic degeneration in vivo by activation of PI3-K pathway and inhibition of p38MAPK. J Neurochem 115:1090–1101. doi:10.1111/j.1471-4159.2010.06766.x
153. Turjanski AG, Vaque JP, Gutkind JS (2007) MAP kinases and the control of nuclear events. Oncogene 26:3240–3253. doi:10.1038/sj.onc.1210415
154. Veglianese P, Lo Coco D, Bao Cutrona M, Magnoni R, Pennacchini D, Pozzi B, Gowing G, Julien JP, Tortarolo M, Bendotti C (2006) Activation of the p38MAPK cascade is associated with upregulation of TNF alpha receptors in the spinal motor neurons of mouse models of familial ALS. Mol Cell Neurosci 31:218–231. doi:10.1016/j.mcn.2005.09.009
155. Vernon AE, LaBonne C (2004) Tumor metastasis: a new twist on epithelial-mesenchymal transitions. Curr Biol 14:R719–R721. doi:10.1016/j.cub.2004.08.048
156. Vetterkind S, Poythress RH, Lin QQ, Morgan KG (2013) Hierarchical scaffolding of an ERK1/2 activation pathway. Cell Commun Signal 11:65. doi:10.1186/1478-811X-11-65
157. Vilotti S, Codrich M, Dal Ferro M, Pinto M, Ferrer I, Collavin L, Gustincich S, Zucchelli S (2012) Parkinson’s disease DJ-1 L166P alters rRNA biogenesis by exclusion of TTRAP from the nucleolus and sequestration into cytoplasmic aggregates via TRAF6. PLoS ONE 7:e35051. doi:10.1371/journal.pone.0035051
158. Vinsant S, Mansfield C, Jimenez-Moreno R, Del Moore VG, Yoshikawa M, Hampton TG, Prevette D, Caress J, Oppenheim RW, Milligan C (2013) Characterization of early pathogenesis in the SOD1(G93A) mouse model of ALS: part I, background and methods. Brain Behav 3:335–350. doi:10.1002/brb3.143
159. Wang IF, Guo BS, Liu YC, Wu CC, Yang CH, Tsai KJ, Shen CK (2012) Autophagy activators rescue and alleviate pathogenesis of a mouse model with proteinopathies of the TAR DNA-binding protein 43. Proc Natl Acad Sci USA 109:15024–15029. doi:10.1073/pnas.1206362109
160. Wang D, Fu Q, Zhou Y, Xu B, Shi Q, Igwe B, Matt L, Hell JW, Wisely EV, Oddo S, Xiang YK (2013) beta2 adrenergic receptor, protein kinase A (PKA) and c-Jun N-terminal kinase (JNK) signaling pathways mediate tau pathology in Alzheimer disease models. J Biol Chem 288:10298–10307. doi:10.1074/jbc.M112.415141
161. Wang KZ, Zhu J, Dagda RK, Uechi G, Cherra SJ 3rd, Gusdon AM, Balasubramani M, Chu CT (2014) ERK-mediated phosphorylation of TFAM downregulates mitochondrial transcription: implications for Parkinson’s disease. Mitochondrion 17:132–140. doi:10.1016/j.mito.2014.04.008
162. Weiss MB, Abel EV, Mayberry MM, Basile KJ, Berger AC, Aplin AE (2012) TWIST1 is an ERK1/2 effector that promotes invasion and regulates MMP-1 expression in human melanoma cells. Cancer Res 72:6382–6392. doi:10.1158/0008-5472.CAN-12-1033
163. Wilkinson K, El Khoury J (2012) Microglial scavenger receptors and their roles in the pathogenesis of Alzheimer’s disease. Int J Alzheimers Dis 2012:489456. doi:10.1155/2012/489456
164. Zhang JY, Selim MA (2012) The role of the c-Jun N-terminal Kinase signaling pathway in skin cancer. Am J Cancer Res 2:691–698
165. Zhang H, Su YJ, Zhou WW, Wang SW, Xu PX, Yu XL, Liu RT (2014) Activated scavenger receptor A promotes glial internalization of abeta. PLoS One 9:e94197. doi:10.1371/journal.pone.0094197
166. Zhu Y, Fotinos A, Mao LL, Atassi N, Zhou EW, Ahmad S, Guan Y, Berry JD, Cudkowicz ME, Wang X (2014) Neuroprotective agents target molecular mechanisms of disease in ALS. Drug Discov Today. doi:10.1016/j.drudis.2014.08.016