identification of neuroprotective genes against alpha - acumen - The ...

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ZK973.5 Neuronal acetylcholine receptor subunit alpha-2 158
Table 4.2. Summary of positive genes from RNAi screen for effectors of α-syn in the daf-2 background based on KOG and/or GO annotations. Category Gene Human ortholog E-value ERAD F26E4.11 (hrdl-1) AMFR 1.90E-39 T27E4.2 (hsp-16.11) Alpha crystallin 2.00E-14 Y38E10A.4 (clec-8) Glycoprotein 340 2.50E-12 ER-Golgi C54H2.5 (sft-4) ERV29 7.80E-88 trafficking F55A4.1 SEC22b 2.30E-47 F57B10.5 emp24/gp25L/p24 2.70E-58 Glutathione- C06A6.5 ERp44 8.30E-75 related C29E4.7 (gsto-1) Glutathione S-transferase 2.00E-32 C54D10.2 C6orf168 8.10E-22 Glycosylation F10C2.5 Glycosyl hydrolase 3.30E-149 T22F3.11 Sialin 7.80E-25 Lysosomal F21F8.7 (asp-6) Aspartyl protease 5.00E-51 function T13B5.3 ACPP 1.80E-38 Y71H2AR.2 Cathepsin L 8.00E-33 Metabolism F01F1.12 ALDOA 2.70E-117 F25B4.1 Aminomethyl transferase 6.90E-101 F38B6.4 GARS/AIRS 1.90E-208 K07C6.3 (cyp-35B2) Cytochrome P450 2C8 4.50E-58 T07D3.7 (alg-2) eIF-2C 0 K10B3.7 (gpd-3) GAPDH 2.80E-136 K10B3.8 (gpd-2) GAPDH 2.80E-136 K12G11.4 (sodh-2) Alcohol dehydrogenase 6.90E-20 T10H4.11 (cyp-34A2) Cytochrome P450 2F1 1.90E-57 Y87G2A.8 (gpi-1) GPI 2.80E-207 W07E11.1 Glutamate synthase 1.80E-11 Signaling C02C2.3 (cup-4) Acetylcholine receptor 2.80E-16 Components C44H4.5 (tap-1) TAB1-like protein 9.50E-12 D1069.3 DRCTNNB1A 2.10E-10 F52F12.3 (mom-4) MAPKKK7 1.20E-38 159
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IDENTIFICATION OF NEUROPROTECTIVE G
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ABSTRACT Recent functional analyses
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E3 Ubiquitin ligase ER Endoplasmic
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RT-PCR Reverse transcriptase polyme
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TAG-278 Temporary assigned gene 278
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p38 Mitogen-activated protein kinas
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ACKNOWLEDGMENTS First and foremost,
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CONTENTS ABSTRACT .................
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a. Abstract .......................
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LIST OF FIGURES 1.1. Schematic repr
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Parkinson disease CHAPTER ONE INTRO
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al., 2006) and torsinA (Cao et al.,
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endoplasmic reticulum (ER) to Golgi
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c-Jun N-terminal kinase and caspase
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lysosomal protease promotes α-syn
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ROS, which may oxidize DA (a neurot
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together, although anti-oxidant act
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multicellular eukaryotic model orga
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C. elegans PD models C. elegans off
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Current studies To investigate gene
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Specific outcomes and future direct
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Corti, O., Hampe, C., Koutnikova, H
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Lautier, C., Goldwurm, S., Dürr, A
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Scherzer, C.R., Jensen, R.V., Gulla
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Willcox, B.J., Donlon, T.A., He, Q.
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Table 1.2. Summary of selected inve
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FIGURE LEGENDS Fig. 1.1. Schematic
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ABSTRACT Genomic multiplication of
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et al., 2003). Maintenance of DA ne
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Pdat-1::FLAG-R05D11.6, Punc-54::DsR
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Biochemicals) and 1:10000 horseradi
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was washed with 100 µl RNase-free
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and effectively discerned via RNAi
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protein. The primary RNAi screen of
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expressing a polyglutamine::GFP fus
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stage (Fig. 2.2B-D). Two genes exhi
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with strong expression localized to
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Our data demonstrating that the C.
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disparate datasets, such as those o
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Driscoll, M., Gerstbrein, B. (2003)
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Singleton, A.B., Farrer, M., Johnso
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Table 2.2. Bioinformatic associatio
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Table 2.4. Results of all genes kno
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C09G12.9 Tumor susceptibility gene
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C32B5.13 Cathepsin H precursor C32B
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D1014.3 Alpha-soluble NSF attachmen
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F22B7.5 DNAJA3, mitochondrial precu
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F40F4.5 Tubulin alpha-ubiquitous ch
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F54F7.5 Serine/threonine kinase 24
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K07A9.2 CAMK1 K07C11.9 Hypothetical
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R74.4 DNAJB1 precursor T01B7.4 Pept
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T22D1.9 PSMD2 T22F3.2 Ubiquitin spe
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Y38F2AL.3 Vacuolar ATP synthase sub
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Y73C8C.8 CENPE variant protein (Fra
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Table 2.5. Summary of RNAi knockdow
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Figure 2.2 91
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Figure 2.4 93
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Figure 2.6 95
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FIGURE LEGENDS Figure 2.1. RNAi kno
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came from genes that were co-expres
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ABSTRACT Multiple Parkinson disease
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vacuoles (mammalian equivalent of l
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neuroprotection when the animals we
Page 127 and 128: To investigate the genetic interact
Page 129 and 130: illustrated that α-syn overexpress
Page 131 and 132: main contributor of α-syn phosphor
Page 133 and 134: Hoozemans, J.J., van Haastert, E.S.
Page 135 and 136: Figure 3.2 115
Page 137 and 138: FIGURE LEGENDS Figure 3.1. RAB3A, R
Page 139 and 140: CHAPTER FOUR RNA INTERFERENCE SCREE
Page 141 and 142: INTRODUCTION Central to Parkinson d
Page 143 and 144: thermotolerance (Lithgow et al., 19
Page 145 and 146: mCherry were transferred onto NGM p
Page 147 and 148: 20°C for 72 hrs. The gravid adults
Page 149 and 150: pathways downstream of DAF-2 exclud
Page 151 and 152: were assayed by growing the RNAi-tr
Page 153 and 154: while DOG treatment enhanced α-syn
Page 155 and 156: enhance α-syn misfolding in a daf-
Page 157 and 158: REFERENCES Bar-On, P., Crews, L., K
Page 159 and 160: Lesage, S., Brice, A. (2009) Hum Mo
Page 161 and 162: Table 4.1. Summary of genes analyze
Page 163 and 164: C12D12.2 Excitatory amino acid tran
Page 165 and 166: C47B2.2 n/a C47C12.6 Amiloride-sens
Page 167 and 168: F18A1.5 Replication protein A F18E3
Page 169 and 170: F46E10.10 Malate dehydrogenase F46E
Page 171 and 172: K08H10.1 Dentin sialophosphoprotein
Page 173 and 174: T05A10.5 Cysteine-rich secretory pr
Page 175 and 176: W03G9.6 Platelet-activating factor
Page 177: Y58G8A.1 Acetylcholine receptor sub
Page 189 and 190: Figure 4.4. Graph illustrating the
Page 191 and 192: in yeast but not in humans. In yeas
Page 193 and 194: kinase that has also been shown to
Page 195 and 196: mir-2/mir-43/mir-250/mir-797 superf
Page 197 and 198: of djr-1.1 and djr-1.2 enhance α-s
Page 199 and 200: expensive, since they require high
Page 201 and 202: Ambros, V. (2001) Cell 107, 823-826
Page 203 and 204: Yi, J., Tang, X.M. (1999) Cell Res
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