Pathological roles of MAPK signaling pathways in human diseases

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Tập 1802 Số 4 - Trang 396-405 - 2010
Eun-Kyung Kim1, Eui‐Ju Choi1
1School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea

Tóm tắt

Từ khóa


Tài liệu tham khảo

McCubrey, 2006, Reactive oxygen species-induced activation of the MAP kinase signaling pathways, Antioxid. Redox Signal., 8, 1775, 10.1089/ars.2006.8.1775

Torii, 2006, ERK MAP kinase in G cell cycle progression and cancer, Cancer Sci., 97, 697, 10.1111/j.1349-7006.2006.00244.x

Dhillon, 2007, MAP kinase signalling pathways in cancer, Oncogene, 26, 3279, 10.1038/sj.onc.1210421

Schaeffer, 1999, Mitogen-activated protein kinases: specific messages from ubiquitous messengers, Mol. Cell. Biol., 19, 2435, 10.1128/MCB.19.4.2435

Morrison, 2003, Regulation of MAP kinase signaling modules by scaffold proteins in mammals, Annu. Rev. Cell Dev. Biol., 19, 91, 10.1146/annurev.cellbio.19.111401.091942

Whitmarsh, 2006, The J.I.P. family of MAPK scaffold proteins, Biochem. Soc. Trans., 34, 828, 10.1042/BST0340828

Davis, 2000, Signal transduction by the JNK group of MAP kinases, Cell, 103, 239, 10.1016/S0092-8674(00)00116-1

Malumbres, 2003, RAS oncogenes: the first 30years, Nat. Rev. Cancer, 3, 459, 10.1038/nrc1097

Uhlik, 2004, Wiring diagrams of MAPK regulation by MEKK1, 2, and 3, Biochem. Cell Biol., 82, 658, 10.1139/o04-114

Cuevas, 2006, MEKK1 controls matrix degradation and tumor cell dissemination during metastasis of polyoma middle-T driven mammary cancer, Oncogene, 25, 4998, 10.1038/sj.onc.1209507

Nagai, 2007, Pathophysiological roles of ASK1-MAP kinase signaling pathways, J. Biochem. Mol. Biol., 40, 1

Giacobini, 2007, One hundred years after the discovery of Alzheimer's disease. A turning point for therapy?, J. Alzheimers Dis., 12, 37, 10.3233/JAD-2007-12105

Reid, 2007, Alzheimer's disease: cholesterol, membrane rafts, isoprenoids and statins, J. Cell. Mol. Med., 11, 383, 10.1111/j.1582-4934.2007.00054.x

Tabaton, 2007, The molecular link between β- and γ-secretase activity on the amyloid β precursor protein, Cell. Mol. Life Sci., 64, 2211, 10.1007/s00018-007-7219-3

Wang, 2008, Microtubule-associated protein tau in development, degeneration and protection of neurons, Prog. Neurobiol., 85, 148, 10.1016/j.pneurobio.2008.03.002

Perez, 2008, Phosphorylated tau in neuritic plaques of APP(sw)/Tau (vlw) transgenic mice and Alzheimer disease, Acta Neuropathol., 116, 409, 10.1007/s00401-008-0420-0

Paulson, 2008, Amyloid plaque and neurofibrillary tangle pathology in a regulatable mouse model of Alzheimer's disease, Am. J. Pathol., 173, 762, 10.2353/ajpath.2008.080175

Dewji, 2005, The structure and functions of the presenilins, Cell. Mol. Life Sci., 62, 1109, 10.1007/s00018-005-4566-9

Jankowsky, 2004, Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ secretase, Hum. Mol. Genet., 13, 159, 10.1093/hmg/ddh019

Placanica, 2009, Gender- and age-dependent γ-secretase activity in mouse brain and its implication in sporadic Alzheimer disease, PLoS One, 4, e5088, 10.1371/journal.pone.0005088

Kojro, 2005, The non-amyloidogenic pathway: structure and function of α-secretases, Subcell. Biochem., 38, 105, 10.1007/0-387-23226-5_5

Sinha, 1999, Purification and cloning of amyloid precursor protein β-secretase from human brain, Nature, 402, 537, 10.1038/990114

Yu, 2000, Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and βAPP processing, Nature, 407, 48, 10.1038/35024009

Vassar, 1999, β-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE, Science, 286, 735, 10.1126/science.286.5440.735

LaFerla, 2007, Intracellular amyloid-β in Alzheimer's disease, Nat. Rev. Neurosci., 8, 499, 10.1038/nrn2168

Caspersen, 2005, Mitochondrial Aβ: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease, FASEB J., 19, 2040, 10.1096/fj.05-3735fje

Melov, 2007, Mitochondrial oxidative stress causes hyperphosphorylation of tau, PLoS One, 2, e536, 10.1371/journal.pone.0000536

Lin, 2006, Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases, Nature, 443, 787, 10.1038/nature05292

Pratico, 2008, Oxidative stress hypothesis in Alzheimer's disease: a reappraisal, Trends Pharmacol. Sci., 29, 609, 10.1016/j.tips.2008.09.001

Zhu, 2002, The role of mitogen-activated protein kinase pathways in Alzheimer's disease, Neurosignals, 11, 270, 10.1159/000067426

Tabner, 2005, Hydrogen peroxide is generated during the very early stages of aggregation of the amyloid peptides implicated in Alzheimer disease and familial British dementia, J. Biol. Chem., 280, 35789, 10.1074/jbc.C500238200

Chiarini, 2009, Calcium-sensing receptor (CaSR) in human brain's pathophysiology: roles in late-onset Alzheimer's disease (LOAD), Curr. Pharm. Biotechnol., 10, 317, 10.2174/138920109787847501

Puig, 2004, Expression of stress-activated kinases c-Jun N-terminal kinase (SAPK/JNK-P) and p38 kinase (p38-P), and tau hyperphosphorylation in neurites surrounding βA plaques in APP Tg2576 mice, Neuropathol. Appl. Neurobiol., 30, 491, 10.1111/j.1365-2990.2004.00569.x

Marques, 2003, Neurotoxic mechanisms caused by the Alzheimer's disease-linked Swedish amyloid precursor protein mutation: oxidative stress, caspases, and the JNK pathway, J. Biol. Chem., 278, 28294, 10.1074/jbc.M212265200

Hashimoto, 2003, Involvement of c-Jun N-terminal kinase in amyloid precursor protein-mediated neuronal cell death, J. Neurochem., 84, 864, 10.1046/j.1471-4159.2003.01585.x

Tamagno, 2005, β-Site APP cleaving enzyme up-regulation induced by 4-hydroxynonenal is mediated by stress-activated protein kinases pathways, J. Neurochem., 92, 628, 10.1111/j.1471-4159.2004.02895.x

Shen, 2008, Hydrogen peroxide promotes Aβ production through JNK-dependent activation of γ-secretase, J. Biol. Chem., 283, 17721, 10.1074/jbc.M800013200

Colombo, 2009, JNK regulates APP cleavage and degradation in a model of Alzheimer's disease, Neurobiol. Dis., 33, 518, 10.1016/j.nbd.2008.12.014

Muresan, 2007, The amyloid-β precursor protein is phosphorylated via distinct pathways during differentiation, mitosis, stress, and degeneration, Mol. Biol. Cell, 18, 3835, 10.1091/mbc.e06-07-0625

Sekine, 2006, The ASK1-MAP kinase signaling in ER stress and neurodegenerative diseases, Curr. Mol. Med., 6, 87, 10.2174/156652406775574541

Peel, 2004, Tau phosphorylation in Alzheimer's disease: potential involvement of an APP-MAP kinase complex, Neuromolecular Med., 5, 205, 10.1385/NMM:5:3:205

Galvan, 2007, Interaction of ASK1 and the β-amyloid precursor protein in a stress-signaling complex, Neurobiol. Dis., 28, 65, 10.1016/j.nbd.2007.06.017

Leyssen, 2005, Amyloid precursor protein promotes post-developmental neurite arborization in the Drosophila brain, EMBO J., 24, 2944, 10.1038/sj.emboj.7600757

Tamagno, 2009, JNK and ERK1/2 pathways have a dual opposite effect on the expression of BACE1, Neurobiol. Aging, 30, 1563, 10.1016/j.neurobiolaging.2007.12.015

Liao, 2004, Tumor necrosis factor-α interleukin-1β and interferon-γ stimulate γ-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway, J. Biol. Chem., 279, 49523, 10.1074/jbc.M402034200

Hashimoto, 2005, Transforming growth factor β2 is a neuronal death-inducing ligand for amyloid-β precursor protein, Mol. Cell. Biol., 25, 9304, 10.1128/MCB.25.21.9304-9317.2005

Gandhi, 2005, Molecular pathogenesis of Parkinson's disease, Hum. Mol. Genet., 14, 2749, 10.1093/hmg/ddi308

Poewe, 2008, Non-motor symptoms in Parkinson's disease, Eur. J. Neurol., 15, 14, 10.1111/j.1468-1331.2008.02056.x

Lesage, 2009, Parkinson's disease: from monogenic forms to genetic susceptibility factors, Hum. Mol. Genet., 18, R48, 10.1093/hmg/ddp012

Spillantini, 1997, α-synuclein in Lewy bodies, Nature, 388, 839, 10.1038/42166

Abeliovich, 2000, Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system, Neuron, 25, 239, 10.1016/S0896-6273(00)80886-7

Polymeropoulos, 1997, Mutation in the α-synuclein gene identified in families with Parkinson's disease, Science, 276, 2045, 10.1126/science.276.5321.2045

Singleton, 2003, α-Synuclein locus triplication causes Parkinson's disease, Science, 302, 841, 10.1126/science.1090278

Chartier-Harlin, 2004, α-Synuclein locus duplication as a cause of familial Parkinson's disease, Lancet, 364, 1167, 10.1016/S0140-6736(04)17103-1

Chen, 2005, α-Synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease, Nat. Neurosci., 8, 657, 10.1038/nn1443

Inglis, 2009, Polo-like kinase 2 (PLK2) phosphorylates α-synuclein at serine 129 in central nervous system, J. Biol. Chem., 284, 2598, 10.1074/jbc.C800206200

Tofaris, 2003, Ubiquitination of α-synuclein in Lewy bodies is a pathological event not associated with impairment of proteasome function, J. Biol. Chem., 278, 44405, 10.1074/jbc.M308041200

Giasson, 2000, Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions, Science, 290, 985, 10.1126/science.290.5493.985

Tofaris, 2006, Pathological changes in dopaminergic nerve cells of the substantia nigra and olfactory bulb in mice transgenic for truncated human α-synuclein(1–120): implications for Lewy body disorders, J. Neurosci., 26, 3942, 10.1523/JNEUROSCI.4965-05.2006

Cookson, 2009, α-Synuclein and neuronal cell death, Mol. Neurodegener., 4, 9, 10.1186/1750-1326-4-9

Saha, 2000, Induction of neuronal death by α-synuclein, Eur. J. Neurosci., 12, 3073, 10.1046/j.1460-9568.2000.00210.x

Hirsch, 2009, Neuroinflammation in Parkinson's disease: a target for neuroprotection?, Lancet Neurol., 8, 382, 10.1016/S1474-4422(09)70062-6

Levy, 2009, Cell death pathways in Parkinson's disease: proximal triggers, distal effectors, and final steps, Apoptosis, 14, 478, 10.1007/s10495-008-0309-3

Miller, 2009, Oxidative and inflammatory pathways in Parkinson's disease, Neurochem. Res., 34, 55, 10.1007/s11064-008-9656-2

Meredith, 2008, Animal models of Parkinson's disease progression, Acta Neuropathol., 115, 385, 10.1007/s00401-008-0350-x

Zhang, 2005, Aggregated α-synuclein activates microglia: a process leading to disease progression in Parkinson's disease, FASEB J., 19, 533, 10.1096/fj.04-2751com

Klegeris, 2008, α-Synuclein activates stress signaling protein kinases in THP-1 cells and microglia, Neurobiol. Aging, 29, 739, 10.1016/j.neurobiolaging.2006.11.013

Klegeris, 2006, α-Synuclein and its disease-causing mutants induce ICAM-1 and IL-6 in human astrocytes and astrocytoma cells, FASEB J., 20, 2000, 10.1096/fj.06-6183com

Devi, 2008, Mitochondrial import and accumulation of α-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain, J. Biol. Chem., 283, 9089, 10.1074/jbc.M710012200

Parihar, 2008, Mitochondrial association of α-synuclein causes oxidative stress, Cell. Mol. Life Sci., 65, 1272, 10.1007/s00018-008-7589-1

Schober, 2004, Classic toxin-induced animal models of Parkinson's disease: 6-OHDA and MPTP, Cell Tissue Res., 318, 215, 10.1007/s00441-004-0938-y

Cicchetti, 2009, Environmental toxins and Parkinson's disease: what have we learned from pesticide-induced animal models?, Trends Pharmacol. Sci., 30, 475, 10.1016/j.tips.2009.06.005

Adam, 2000, Pesticide use linked to Parkinson's disease, Nature, 408, 125, 10.1038/35041740

Hatcher, 2008, Parkinson's disease and pesticides: a toxicological perspective, Trends Pharmacol. Sci., 29, 322, 10.1016/j.tips.2008.03.007

Beal, 2001, Experimental models of Parkinson's disease, Nat. Rev. Neurosci., 2, 325, 10.1038/35072550

Karunakaran, 2007, Activation of apoptosis signal regulating kinase 1 (ASK1) and translocation of death-associated protein, Daxx, in substantia nigra pars compacta in a mouse model of Parkinson's disease: protection by α-lipoic acid, FASEB J., 21, 2226, 10.1096/fj.06-7580com

Saporito, 2000, MPTP activates c-Jun NH(2)-terminal kinase (JNK) and its upstream regulatory kinase MKK4 in nigrostriatal neurons in vivo, J. Neurochem., 75, 1200, 10.1046/j.1471-4159.2000.0751200.x

Ouyang, 2006, Critical role of ASK1 in the 6-hydroxydopamine-induced apoptosis in human neuroblastoma SH-SY5Y cells, J. Neurochem., 97, 234, 10.1111/j.1471-4159.2006.03730.x

Silva, 2005, Mixed lineage kinase-c-jun N-terminal kinase signaling pathway: a new therapeutic target in Parkinson's disease, Mov. Disord., 20, 653, 10.1002/mds.20390

Mathiasen, 2004, Inhibition of mixed lineage kinase 3 attenuates MPP+-induced neurotoxicity in SH-SY5Y cells, Brain Res., 1003, 86, 10.1016/j.brainres.2003.11.073

Chipuk, 2008, How do BCL-2 proteins induce mitochondrial outer membrane permeabilization?, Trends Cell Biol., 18, 157, 10.1016/j.tcb.2008.01.007

Karunakaran, 2008, Selective activation of p38 mitogen-activated protein kinase in dopaminergic neurons of substantia nigra leads to nuclear translocation of p53 in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-treated mice, J. Neurosci., 28, 12500, 10.1523/JNEUROSCI.4511-08.2008

Rawal, 2007, Inhibition of JNK increases survival of transplanted dopamine neurons in Parkinsonian rats, Cell Death Differ., 14, 381, 10.1038/sj.cdd.4402010

Pan, 2007, Expression of FasL and its interaction with Fas are mediated by c-Jun N-terminal kinase (JNK) pathway in 6-OHDA-induced rat model of Parkinson disease, Neurosci. Lett., 428, 82, 10.1016/j.neulet.2007.09.032

Newhouse, 2004, Rotenone-induced apoptosis is mediated by p38 and JNK MAP kinases in human dopaminergic SH-SY5Y cells, Toxicol. Sci., 79, 137, 10.1093/toxsci/kfh089

Hsuan, 2006, Basic fibroblast growth factor protects against rotenone-induced dopaminergic cell death through activation of extracellular signal-regulated kinases 1/2 and phosphatidylinositol-3 kinase pathways, J. Neurosci., 26, 4481, 10.1523/JNEUROSCI.4922-05.2006

Peng, 2004, The herbicide paraquat induces dopaminergic nigral apoptosis through sustained activation of the JNK pathway, J. Biol. Chem., 279, 32626, 10.1074/jbc.M404596200

Klintworth, 2007, Activation of c-Jun N-terminal protein kinase is a common mechanism underlying paraquat- and rotenone-induced dopaminergic cell apoptosis, Toxicol. Sci., 97, 149, 10.1093/toxsci/kfm029

Ramachandiran, 2007, Divergent mechanisms of paraquat, MPP+, and rotenone toxicity: oxidation of thioredoxin and caspase-3 activation, Toxicol. Sci., 95, 163, 10.1093/toxsci/kfl125

Resnick, 2004, Targeting JNK3 for the treatment of neurodegenerative disorders, Drug Discov. Today, 9, 932, 10.1016/S1359-6446(04)03251-9

Saporito, 2002, Discovery of CEP-1347/KT-7515, an inhibitor of the JNK/SAPK pathway for the treatment of neurodegenerative diseases, Prog. Med. Chem., 40, 23, 10.1016/S0079-6468(08)70081-X

2007, Mixed lineage kinase inhibitor CEP-1347 fails to delay disability in early Parkinson disease, Neurology, 69, 1480, 10.1212/01.wnl.0000277648.63931.c0

Kuan, 2005, Targeting the JNK signaling pathway for stroke and Parkinson's diseases therapy, Curr. Drug Targets. CNS Neurol. Disord., 4, 63, 10.2174/1568007053005145

Guo, 2006, Leucine-rich repeat kinase 2: relevance to Parkinson's disease, Int. J. Biochem. Cell Biol., 38, 1469, 10.1016/j.biocel.2006.02.009

Zimprich, 2004, Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology, Neuron, 44, 601, 10.1016/j.neuron.2004.11.005

West, 2005, Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity, Proc. Natl. Acad. Sci. U. S. A., 102, 16842, 10.1073/pnas.0507360102

White, 2007, MAPK-pathway activity, Lrrk2 G2019S, and Parkinson's disease, J. Neurosci. Res., 85, 1288, 10.1002/jnr.21240

Gloeckner, 2009, The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro, J. Neurochem., 109, 959, 10.1111/j.1471-4159.2009.06024.x

Safadi, 2007, A disease state mutation unfolds the parkin ubiquitin-like domain, Biochemistry, 46, 14162, 10.1021/bi7016969

Staropoli, 2003, Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity, Neuron, 37, 735, 10.1016/S0896-6273(03)00084-9

Chung, 2001, Parkin ubiquitinates the α-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease, Nat. Med., 7, 1144, 10.1038/nm1001-1144

Lim, 2007, Parkin interacts with LIM Kinase 1 and reduces its cofilin-phosphorylation activity via ubiquitination, Exp. Cell Res., 313, 2858, 10.1016/j.yexcr.2007.04.016

Petrucelli, 2002, Parkin protects against the toxicity associated with mutant α-synuclein: proteasome dysfunction selectively affects catecholaminergic neurons, Neuron, 36, 1007, 10.1016/S0896-6273(02)01125-X

Jiang, 2004, Parkin protects human dopaminergic neuroblastoma cells against dopamine-induced apoptosis, Hum. Mol. Genet., 13, 1745, 10.1093/hmg/ddh180

Cha, 2005, Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila, Proc. Natl. Acad. Sci. U. S. A., 102, 10345, 10.1073/pnas.0500346102

Narendra, 2008, Parkin is recruited selectively to impaired mitochondria and promotes their autophagy, J. Cell Biol., 183, 795, 10.1083/jcb.200809125

McBride, 2008, Parkin mitochondria in the autophagosome, J. Cell Biol., 183, 757, 10.1083/jcb.200810184

Cesari, 2003, Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27, Proc. Natl. Acad. Sci. U. S. A., 100, 5956, 10.1073/pnas.0931262100

Staropoli, 2008, Tumorigenesis and neurodegeneration: two sides of the same coin?, Bioessays, 30, 719, 10.1002/bies.20784

Xiong, 2009, Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation, J. Clin. Invest., 119, 650, 10.1172/JCI37617

Mills, 2008, Biochemical aspects of the neuroprotective mechanism of PTEN-induced kinase-1 (PINK1), J. Neurochem., 105, 18, 10.1111/j.1471-4159.2008.05249.x

Park, 2006, Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin, Nature, 441, 1157, 10.1038/nature04788

Andres-Mateos, 2007, DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase, Proc. Natl. Acad. Sci. U. S. A., 104, 14807, 10.1073/pnas.0703219104

Xu, 2005, The Parkinson's disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis, Hum. Mol. Genet., 14, 1231, 10.1093/hmg/ddi134

Junn, 2009, Mitochondrial localization of DJ-1 leads to enhanced neuroprotection, J. Neurosci. Res., 87, 123, 10.1002/jnr.21831

Batelli, 2008, DJ-1 modulates α-synuclein aggregation state in a cellular model of oxidative stress: relevance for Parkinson's disease and involvement of HSP70, PLoS One, 3, e1884, 10.1371/journal.pone.0001884

Waak, 2009, Regulation of astrocyte inflammatory responses by the Parkinson's disease-associated gene DJ-1, FASEB J., 23, 2478, 10.1096/fj.08-125153

Mo, 2008, DJ-1 modulates UV-induced oxidative stress signaling through the suppression of MEKK1 and cell death, Cell Death Differ., 15, 1030, 10.1038/cdd.2008.26

Zucchelli, 2009, Aggresome-forming TTRAP mediates pro-apoptotic properties of Parkinson's disease-associated DJ-1 missense mutations, Cell Death Differ., 16, 428, 10.1038/cdd.2008.169

Vande Walle, 2008, The mitochondrial serine protease HtrA2/Omi: an overview, Cell Death Differ., 15, 453, 10.1038/sj.cdd.4402291

Martins, 2004, Neuroprotective role of the Reaper-related serine protease HtrA2/Omi revealed by targeted deletion in mice, Mol. Cell. Biol., 24, 9848, 10.1128/MCB.24.22.9848-9862.2004

Strauss, 2005, Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease, Hum. Mol. Genet., 14, 2099, 10.1093/hmg/ddi215

Yun, 2008, Loss-of-function analysis suggests that Omi/HtrA2 is not an essential component of the PINK1/PARKIN pathway in vivo, J. Neurosci., 28, 14500, 10.1523/JNEUROSCI.5141-08.2008

Plun-Favreau, 2007, The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1, Nat. Cell Biol., 9, 1243, 10.1038/ncb1644

Pasinelli, 2006, Molecular biology of amyotrophic lateral sclerosis: insights from genetics, Nat. Rev. Neurosci., 7, 710, 10.1038/nrn1971

Vucic, 2009, Pathophysiology of neurodegeneration in familial amyotrophic lateral sclerosis, Curr. Mol. Med., 9, 255, 10.2174/156652409787847173

Mackenzie, 2007, Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations, Ann. Neurol., 61, 427, 10.1002/ana.21147

Kwiatkowski, 2009, Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis, Science, 323, 1205, 10.1126/science.1166066

Lagier-Tourenne, 2009, Rethinking ALS: the FUS about TDP-43, Cell, 136, 1001, 10.1016/j.cell.2009.03.006

Shaw, 2005, Molecular and cellular pathways of neurodegeneration in motor neurone disease, J. Neurol. Neurosurg. Psychiatry, 76, 1046, 10.1136/jnnp.2004.048652

Gurney, 1994, Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation, Science, 264, 1772, 10.1126/science.8209258

Bendotti, 2005, Inter- and intracellular signaling in amyotrophic lateral sclerosis: role of p38 mitogen-activated protein kinase, Neurodegener. Dis., 2, 128, 10.1159/000089617

Tortarolo, 2003, Persistent activation of p38 mitogen-activated protein kinase in a mouse model of familial amyotrophic lateral sclerosis correlates with disease progression, Mol. Cell. Neurosci., 23, 180, 10.1016/S1044-7431(03)00022-8

Holasek, 2005, Activation of the stress-activated MAP kinase, p38, but not JNK in cortical motor neurons during early presymptomatic stages of amyotrophic lateral sclerosis in transgenic mice, Brain Res., 1045, 185, 10.1016/j.brainres.2005.03.037

Dewil, 2007, Inhibition of p38 mitogen activated protein kinase activation and mutant SOD1(G93A)-induced motor neuron death, Neurobiol. Dis., 26, 332, 10.1016/j.nbd.2006.12.023

Bendotti, 2004, Activated p38MAPK is a novel component of the intracellular inclusions found in human amyotrophic lateral sclerosis and mutant SOD1 transgenic mice, J. Neuropathol. Exp. Neurol., 63, 113, 10.1093/jnen/63.2.113

Ackerley, 2004, p38α stress-activated protein kinase phosphorylates neurofilaments and is associated with neurofilament pathology in amyotrophic lateral sclerosis, Mol. Cell. Neurosci., 26, 354, 10.1016/j.mcn.2004.02.009

Brownlees, 2000, Phosphorylation of neurofilament heavy chain side-arms by stress activated protein kinase-1b/Jun N-terminal kinase-3, J. Cell Sci., 113, 401, 10.1242/jcs.113.3.401

Raoul, 2002, Motoneuron death triggered by a specific pathway downstream of Fas. Potentiation by ALS-linked SOD1 mutations, Neuron, 35, 1067, 10.1016/S0896-6273(02)00905-4

Raoul, 2006, Chronic activation in presymptomatic amyotrophic lateral sclerosis (ALS) mice of a feedback loop involving Fas, Daxx, and FasL, Proc. Natl. Acad. Sci. U. S. A., 103, 6007, 10.1073/pnas.0508774103

Meusser, 2005, ERAD: the long road to destruction, Nat. Cell Biol., 7, 766, 10.1038/ncb0805-766

Nishitoh, 2008, ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1, Genes Dev., 22, 1451, 10.1101/gad.1640108

Nishitoh, 2002, ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats, Genes Dev., 16, 1345, 10.1101/gad.992302

Boutros, 2008, Mitogen-activated protein (MAP) kinase/MAP kinase phosphatase regulation: roles in cell growth, death, and cancer, Pharmacol. Rev., 60, 261, 10.1124/pr.107.00106

Schubbert, 2007, Hyperactive Ras in developmental disorders and cancer, Nat. Rev. Cancer, 7, 295, 10.1038/nrc2109

Haigis, 2008, Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon, Nat. Genet., 40, 600, 10.1038/ng.115

Calcagno, 2008, Oncogenic K-ras promotes early carcinogenesis in the mouse proximal colon, Int. J. Cancer, 122, 2462, 10.1002/ijc.23383

Voisin, 2008, Activation of MEK1 or MEK2 isoform is sufficient to fully transform intestinal epithelial cells and induce the formation of metastatic tumors, BMC Cancer, 8, 337, 10.1186/1471-2407-8-337

Halilovic, 2008, Therapeutic strategies for inhibiting oncogenic BRAF signaling, Curr. Opin. Pharmacol., 8, 419, 10.1016/j.coph.2008.06.014

Wan, 2004, Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF, Cell, 116, 855, 10.1016/S0092-8674(04)00215-6

Rushworth, 2006, Regulation and role of Raf-1/B-Raf heterodimerization, Mol. Cell. Biol., 26, 2262, 10.1128/MCB.26.6.2262-2272.2006

Zebisch, 2006, Two transforming C-RAF germ-line mutations identified in patients with therapy-related acute myeloid leukemia, Cancer Res., 66, 3401, 10.1158/0008-5472.CAN-05-0115

Huang, 2004, MAP kinases and cell migration, J. Cell Sci., 117, 4619, 10.1242/jcs.01481

Chakraborti, 2003, Regulation of matrix metalloproteinases: an overview, Mol. Cell. Biochem., 253, 269, 10.1023/A:1026028303196

Balmanno, 2009, Tumour cell survival signalling by the ERK1/2 pathway, Cell Death Differ., 16, 368, 10.1038/cdd.2008.148

Ley, 2003, Activation of the ERK1/2 signaling pathway promotes phosphorylation and proteasome-dependent degradation of the BH3-only protein, Bim, J. Biol. Chem., 278, 18811, 10.1074/jbc.M301010200

Fu, 2008, FOXOs, cancer and regulation of apoptosis, Oncogene, 27, 2312, 10.1038/onc.2008.24

Warr, 2008, Unique biology of Mcl-1: therapeutic opportunities in cancer, Curr. Mol. Med., 8, 138, 10.2174/156652408783769580

Chaparro, 2008, Review article: pharmacological therapy for hepatocellular carcinoma with sorafenib and other oral agents, Aliment. Pharmacol. Ther., 28, 1269, 10.1111/j.1365-2036.2008.03857.x

Hynes, 2009, ErbB receptors and signaling pathways in cancer, Curr. Opin. Cell Biol., 21, 177, 10.1016/j.ceb.2008.12.010

Nagahara, 2005, Somatic mutations of epidermal growth factor receptor in colorectal carcinoma, Clin. Cancer Res., 11, 1368, 10.1158/1078-0432.CCR-04-1894

Dy, 2009, Emerging therapeutic targets in non-small cell lung cancer, Proc. Am. Thorac. Soc., 6, 218, 10.1513/pats.200808-099LC

Paez, 2004, EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy, Science, 304, 1497, 10.1126/science.1099314

Zhu, 2008, Better survival with EGFR exon 19 than exon 21 mutations in gefitinib-treated non-small cell lung cancer patients is due to differential inhibition of downstream signals, Cancer Lett., 265, 307, 10.1016/j.canlet.2008.02.064

Engelman, 2008, Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers, Nat. Med., 14, 1351, 10.1038/nm.1890

Downward, 2008, Targeting RAS and PI3K in lung cancer, Nat. Med., 14, 1315, 10.1038/nm1208-1315

Bogoyevitch, 2004, Targeting the JNK MAPK cascade for inhibition: basic science and therapeutic potential, Biochim. Biophys. Acta, 1697, 89, 10.1016/j.bbapap.2003.11.016

Churcher, 2006, Tau therapeutic strategies for the treatment of Alzheimer's disease, Curr. Top. Med. Chem., 6, 579, 10.2174/156802606776743057

Munoz, 2007, A novel p38α MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model, J. Neuroinflammation, 4, 21, 10.1186/1742-2094-4-21

Colombo, 2007, The TAT-JNK inhibitor peptide interferes with β amyloid protein stability, Cell Death Differ., 14, 1845, 10.1038/sj.cdd.4402202

Olanow, 2008, Why have we failed to achieve neuroprotection in Parkinson's disease?, Ann. Neurol., 64, S101

Hudkins, 2008, Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3, 4-a]pyrrolo[3, 4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models, J. Med. Chem., 51, 5680, 10.1021/jm8005838

Beloueche-Babari, 2005, Magnetic resonance spectroscopy monitoring of mitogen-activated protein kinase signaling inhibition, Cancer Res., 65, 3356, 10.1158/10.1158/0008-5472.CAN-03-2981

Van Den Blink, 2002, From extracellular to intracellular targets, inhibiting MAP kinases in treatment of Crohn's disease, Ann. N. Y. Acad. Sci., 973, 349, 10.1111/j.1749-6632.2002.tb04664.x

Torres, 2006, Mechanisms of disease: autosomal dominant and recessive polycystic kidney diseases, Nat. Clin. Pract. Nephrol., 2, 40, 10.1038/ncpneph0070

Aoki, 2008, The RAS/MAPK syndromes: novel roles of the RAS pathway in human genetic disorders, Hum. Mutat., 29, 992, 10.1002/humu.20748