Genome wide analysis reveals heparan sulfate epimerase modulates TDP-43 proteinopathy
Autoři:
Nicole F. Liachko aff001; Aleen D. Saxton aff001; Pamela J. McMillan aff003; Timothy J. Strovas aff001; C. Dirk Keene aff004; Thomas D. Bird aff001; Brian C. Kraemer aff001
Působiště autorů:
Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, United States of America
aff001; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington, United States of America
aff002; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, United States of America
aff003; Department of Pathology, University of Washington, Seattle, Washington, United States of America
aff004; Department of Neurology, University of Washington, Seattle, Washington, United States of America
aff005; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington, United States of America
aff006
Vyšlo v časopise:
Genome wide analysis reveals heparan sulfate epimerase modulates TDP-43 proteinopathy. PLoS Genet 15(12): e32767. doi:10.1371/journal.pgen.1008526
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008526
Souhrn
Pathological phosphorylated TDP-43 protein (pTDP) deposition drives neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP). However, the cellular and genetic mechanisms at work in pathological TDP-43 toxicity are not fully elucidated. To identify genetic modifiers of TDP-43 neurotoxicity, we utilized a Caenorhabditis elegans model of TDP-43 proteinopathy expressing human mutant TDP-43 pan-neuronally (TDP-43 tg). In TDP-43 tg C. elegans, we conducted a genome-wide RNAi screen covering 16,767 C. elegans genes for loss of function genetic suppressors of TDP-43-driven motor dysfunction. We identified 46 candidate genes that when knocked down partially ameliorate TDP-43 related phenotypes; 24 of these candidate genes have conserved homologs in the human genome. To rigorously validate the RNAi findings, we crossed the TDP-43 transgene into the background of homozygous strong genetic loss of function mutations. We have confirmed 9 of the 24 candidate genes significantly modulate TDP-43 transgenic phenotypes. Among the validated genes we focused on, one of the most consistent genetic modifier genes protecting against pTDP accumulation and motor deficits was the heparan sulfate-modifying enzyme hse-5, the C. elegans homolog of glucuronic acid epimerase (GLCE). We found that knockdown of human GLCE in cultured human cells protects against oxidative stress induced pTDP accumulation. Furthermore, expression of glucuronic acid epimerase is significantly decreased in the brains of FTLD-TDP cases relative to normal controls, demonstrating the potential disease relevance of the candidate genes identified. Taken together these findings nominate glucuronic acid epimerase as a novel candidate therapeutic target for TDP-43 proteinopathies including ALS and FTLD-TDP.
Klíčová slova:
Amyotrophic lateral sclerosis – Caenorhabditis elegans – Genetic screens – Motor neurons – Motor proteins – Phosphorylation – RNA interference – Suppressor genes
Zdroje
1. Tan RH, Ke YD, Ittner LM, Halliday GM. ALS/FTLD: experimental models and reality. Acta Neuropathologica. 2017:1–20. doi: 10.1007/s00401-016-1666-6 28058507
2. Mann DMA, Snowden JS. Frontotemporal lobar degeneration: Pathogenesis, pathology and pathways to phenotype. Brain Pathol. 2017. doi: 10.1111/bpa.12486 28100023.
3. Chornenkyy Y, Fardo DW, Nelson PT. Tau and TDP-43 proteinopathies: kindred pathologic cascades and genetic pleiotropy. Lab Invest. 2019. doi: 10.1038/s41374-019-0196-y 30742063.
4. Wilson RS, Yu L, Trojanowski JQ, Chen EY, Boyle PA, Bennett DA, et al. TDP-43 pathology, cognitive decline, and dementia in old age. JAMA Neurol. 2013;70(11):1418–24. doi: 10.1001/jamaneurol.2013.3961 24080705
5. James BD, Wilson RS, Boyle PA, Trojanowski JQ, Bennett DA, Schneider JA. TDP-43 stage, mixed pathologies, and clinical Alzheimer’s-type dementia. Brain. 2016;139(11):2983–93. doi: 10.1093/brain/aww224 27694152
6. Cohen TJ, Hwang AW, Restrepo CR, Yuan CX, Trojanowski JQ, Lee VM. An acetylation switch controls TDP-43 function and aggregation propensity. Nat Commun. 2015;6:5845. doi: 10.1038/ncomms6845 25556531
7. Seyfried NT, Gozal YM, Dammer EB, Xia Q, Duong DM, Cheng D, et al. Multiplex SILAC analysis of a cellular TDP-43 proteinopathy model reveals protein inclusions associated with SUMOylation and diverse polyubiquitin chains. Mol Cell Proteomics. 2010;9(4):705–18. Epub 2010/01/0610. doi: 10.1074/mcp.M800390-MCP200 20047951.
8. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006;314(5796):130–3. Epub 2006/10/07. doi: 10.1126/science.1134108 17023659.
9. Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H, et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun. 2006;351(3):602–11. Epub 2006/11/07. doi: 10.1016/j.bbrc.2006.10.093 17084815.
10. Neumann M, Kwong LK, Lee EB, Kremmer E, Flatley A, Xu Y, et al. Phosphorylation of S409/410 of TDP-43 is a consistent feature in all sporadic and familial forms of TDP-43 proteinopathies. Acta Neuropathol. 2009;117(2):137–49. doi: 10.1007/s00401-008-0477-9 19125255
11. Liachko NF, McMillan PJ, Guthrie CR, Bird TD, Leverenz JB, Kraemer BC. CDC7 inhibition blocks pathological TDP-43 phosphorylation and neurodegeneration. Ann Neurol. 2013;74(1):39–52. doi: 10.1002/ana.23870 23424178
12. Ayala YM, Zago P, D’Ambrogio A, Xu YF, Petrucelli L, Buratti E, et al. Structural determinants of the cellular localization and shuttling of TDP-43. J Cell Sci. 2008;121(Pt 22):3778–85. Epub 2008/10/30. doi: 10.1242/jcs.038950 18957508.
13. Hasegawa M, Arai T, Nonaka T, Kametani F, Yoshida M, Hashizume Y, et al. Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Ann Neurol. 2008;64(1):60–70. doi: 10.1002/ana.21425 18546284
14. Zhang YJ, Gendron TF, Xu YF, Ko LW, Yen SH, Petrucelli L. Phosphorylation regulates proteasomal-mediated degradation and solubility of TAR DNA binding protein-43 C-terminal fragments. Mol Neurodegener. 2010;5:33. Epub 2010/09/02. doi: 10.1186/1750-1326-5-33 20804554
15. Brady OA, Meng P, Zheng Y, Mao Y, Hu F. Regulation of TDP-43 aggregation by phosphorylation and p62/SQSTM1. J Neurochem. 2011;116(2):248–59. Epub 2010/11/11. doi: 10.1111/j.1471-4159.2010.07098.x 21062285.
16. Liachko NF, Guthrie CR, Kraemer BC. Phosphorylation Promotes Neurotoxicity in a Caenorhabditis elegans Model of TDP-43 Proteinopathy. J Neurosci. 2010;30(48):16208–19. Epub 2010/12/03. doi: 10.1523/JNEUROSCI.2911-10.2010 21123567.
17. Li HR, Chiang WC, Chou PC, Wang WJ, Huang JR. TAR DNA-binding protein 43 (TDP-43) liquid-liquid phase separation is mediated by just a few aromatic residues. J Biol Chem. 2018;293(16):6090–8. doi: 10.1074/jbc.AC117.001037 29511089
18. Conicella AE, Zerze GH, Mittal J, Fawzi NL. ALS Mutations Disrupt Phase Separation Mediated by alpha-Helical Structure in the TDP-43 Low-Complexity C-Terminal Domain. Structure. 2016;24(9):1537–49. doi: 10.1016/j.str.2016.07.007 27545621
19. Ritson GP, Custer SK, Freibaum BD, Guinto JB, Geffel D, Moore J, et al. TDP-43 mediates degeneration in a novel Drosophila model of disease caused by mutations in VCP/p97. J Neurosci. 2010;30(22):7729–39. Epub 2010/06/04. doi: 10.1523/JNEUROSCI.5894-09.2010 20519548
20. Nollen EA, Garcia SM, van Haaften G, Kim S, Chavez A, Morimoto RI, et al. Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation. Proc Natl Acad Sci U S A. 2004;101(17):6403–8. doi: 10.1073/pnas.0307697101 15084750
21. Kraemer BC, Burgess JK, Chen JH, Thomas JH, Schellenberg GD. Molecular pathways that influence human tau-induced pathology in Caenorhabditis elegans. Hum Mol Genet. 2006;15(9):1483–96. doi: 10.1093/hmg/ddl067 16600994
22. Karsten SL, Sang TK, Gehman LT, Chatterjee S, Liu J, Lawless GM, et al. A genomic screen for modifiers of tauopathy identifies puromycin-sensitive aminopeptidase as an inhibitor of tau-induced neurodegeneration. Neuron. 2006;51(5):549–60. doi: 10.1016/j.neuron.2006.07.019 16950154
23. Dimitriadi M, Sleigh JN, Walker A, Chang HC, Sen A, Kalloo G, et al. Conserved genes act as modifiers of invertebrate SMN loss of function defects. PLoS Genet. 2010;6(10):e1001172. doi: 10.1371/journal.pgen.1001172 21124729
24. Manzo E, O’Conner AG, Barrows JM, Shreiner DD, Birchak GJ, Zarnescu DC. Medium-Chain Fatty Acids, Beta-Hydroxybutyric Acid and Genetic Modulation of the Carnitine Shuttle Are Protective in a Drosophila Model of ALS Based on TDP-43. Front Mol Neurosci. 2018;11:182. doi: 10.3389/fnmol.2018.00182 29904341
25. Wang J, Farr GW, Hall DH, Li F, Furtak K, Dreier L, et al. An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of Caenorhabditis elegans. PLoS Genet. 2009;5(1):e1000350. doi: 10.1371/journal.pgen.1000350 19165329
26. Berson A, Goodman LD, Sartoris AN, Otte CG, Aykit JA, Lee VM, et al. Drosophila Ref1/ALYREF regulates transcription and toxicity associated with ALS/FTD disease etiologies. Acta Neuropathol Commun. 2019;7(1):65. doi: 10.1186/s40478-019-0710-x 31036086.
27. Elden AC, Kim HJ, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature. 2010;466(7310):1069–75. doi: 10.1038/nature09320 20740007
28. Armakola M, Higgins MJ, Figley MD, Barmada SJ, Scarborough EA, Diaz Z, et al. Inhibition of RNA lariat debranching enzyme suppresses TDP-43 toxicity in ALS disease models. Nat Genet. 2012;44(12):1302–9. doi: 10.1038/ng.2434 23104007
29. Kim SH, Zhan L, Hanson KA, Tibbetts RS. High-content RNAi screening identifies the Type 1 inositol triphosphate receptor as a modifier of TDP-43 localization and neurotoxicity. Hum Mol Genet. 2012;21(22):4845–56. doi: 10.1093/hmg/dds321 22872699
30. Sreedharan J, Neukomm LJ, Brown RH, Jr., Freeman MR. Age-Dependent TDP-43-Mediated Motor Neuron Degeneration Requires GSK3, hat-trick, and xmas-2. Curr Biol. 2015;25(16):2130–6. doi: 10.1016/j.cub.2015.06.045 26234214
31. Zhan L, Xie Q, Tibbetts RS. Opposing roles of p38 and JNK in a Drosophila model of TDP-43 proteinopathy reveal oxidative stress and innate immunity as pathogenic components of neurodegeneration. Hum Mol Genet. 2015;24(3):757–72. doi: 10.1093/hmg/ddu493 25281658
32. Appocher C, Mohagheghi F, Cappelli S, Stuani C, Romano M, Feiguin F, et al. Major hnRNP proteins act as general TDP-43 functional modifiers both in Drosophila and human neuronal cells. Nucleic Acids Res. 2017;45(13):8026–45. doi: 10.1093/nar/gkx477 28575377
33. Pons M, Prieto S, Miguel L, Frebourg T, Campion D, Sune C, et al. Identification of TCERG1 as a new genetic modulator of TDP-43 production in Drosophila. Acta Neuropathol Commun. 2018;6(1):138. doi: 10.1186/s40478-018-0639-5 30541625
34. White JG, Southgate E, Thomson JN, Brenner S. The structure of the nervous system of the nematode Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci. 1986;314(1165):1–340. doi: 10.1098/rstb.1986.0056 22462104.
35. Kamath RS F A, Dong Y, Poulin G, Durbin R, Gotta M, Kanapin A, Le Bot N, Moreno S, Sohrmann M, Welchman DP, Zipperlen P, Ahringer J. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature. 2003;421((6920)):231–7. doi: 10.1038/nature01278 12529635
36. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990;215(3):403–10. Epub 1990/10/05. doi: 10.1016/S0022-2836(05)80360-2 2231712.
37. Rhiner C, Gysi S, Frohli E, Hengartner MO, Hajnal A. Syndecan regulates cell migration and axon guidance in C. elegans. Development. 2005;132(20):4621–33. doi: 10.1242/dev.02042 16176946.
38. Bulow HE, Hobert O. Differential sulfations and epimerization define heparan sulfate specificity in nervous system development. Neuron. 2004;41(5):723–36. doi: 10.1016/s0896-6273(04)00084-4 15003172.
39. Lazaro-Pena MI, Diaz-Balzac CA, Bulow HE, Emmons SW. Synaptogenesis Is Modulated by Heparan Sulfate in Caenorhabditis elegans. Genetics. 2018;209(1):195–208. doi: 10.1534/genetics.118.300837 29559501
40. Sarrazin S, Lamanna WC, Esko JD. Heparan sulfate proteoglycans. Cold Spring Harb Perspect Biol. 2011;3(7). doi: 10.1101/cshperspect.a004952 21690215
41. Jia J, Maccarana M, Zhang X, Bespalov M, Lindahl U, Li JP. Lack of L-iduronic acid in heparan sulfate affects interaction with growth factors and cell signaling. J Biol Chem. 2009;284(23):15942–50. doi: 10.1074/jbc.M809577200 19336402
42. Li JP, Gong F, Hagner-McWhirter A, Forsberg E, Abrink M, Kisilevsky R, et al. Targeted disruption of a murine glucuronyl C5-epimerase gene results in heparan sulfate lacking L-iduronic acid and in neonatal lethality. J Biol Chem. 2003;278(31):28363–6. doi: 10.1074/jbc.C300219200 12788935.
43. Li J, Fang J, Qin Y, Liao W, Liu H, Zhou Y, et al. GLCE regulates PC12 cell neuritogenesis induced by nerve growth factor through activating SMAD/ID3 signalling. Biochem J. 2014;459(2):405–15. doi: 10.1042/BJ20131360 24499487.
44. McIntire SL, Reimer RJ, Schuske K, Edwards RH, Jorgensen EM. Identification and characterization of the vesicular GABA transporter. Nature. 1997;389(6653):870–6. doi: 10.1038/39908 9349821.
45. Mahoney TR, Luo S, Nonet ML. Analysis of synaptic transmission in Caenorhabditis elegans using an aldicarb-sensitivity assay. Nat Protoc. 2006;1(4):1772–7. doi: 10.1038/nprot.2006.281 17487159.
46. Iguchi Y, Katsuno M, Takagi S, Ishigaki S, Niwa J, Hasegawa M, et al. Oxidative stress induced by glutathione depletion reproduces pathological modifications of TDP-43 linked to TDP-43 proteinopathies. Neurobiol Dis. 2012;45(3):862–70. doi: 10.1016/j.nbd.2011.12.002 22198567.
47. Nicolas A, Kenna KP, Renton AE, Ticozzi N, Faghri F, Chia R, et al. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene. Neuron. 2018;97(6):1268–83 e6. doi: 10.1016/j.neuron.2018.02.027 29566793
48. Antonicka H, Leary SC, Guercin GH, Agar JN, Horvath R, Kennaway NG, et al. Mutations in COX10 result in a defect in mitochondrial heme A biosynthesis and account for multiple, early-onset clinical phenotypes associated with isolated COX deficiency. Hum Mol Genet. 2003;12(20):2693–702. doi: 10.1093/hmg/ddg284 12928484.
49. Timmerman V, Strickland AV, Zuchner S. Genetics of Charcot-Marie-Tooth (CMT) Disease within the Frame of the Human Genome Project Success. Genes (Basel). 2014;5(1):13–32. doi: 10.3390/genes5010013 24705285
50. Tamiya G, Makino S, Hayashi M, Abe A, Numakura C, Ueki M, et al. A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-Marie-Tooth disease. Am J Hum Genet. 2014;95(3):294–300. doi: 10.1016/j.ajhg.2014.07.013 25152455
51. Fiermonte G, Palmieri L, Todisco S, Agrimi G, Palmieri F, Walker JE. Identification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms. J Biol Chem. 2002;277(22):19289–94. doi: 10.1074/jbc.M201572200 11897791.
52. Magoulas PL, El-Hattab AW. Systemic primary carnitine deficiency: an overview of clinical manifestations, diagnosis, and management. Orphanet J Rare Dis. 2012;7:68. doi: 10.1186/1750-1172-7-68 22989098
53. Parker-Duffen JL, Nakamura K, Silver M, Zuriaga MA, MacLauchlan S, Aprahamian TR, et al. Divergent roles for adiponectin receptor 1 (AdipoR1) and AdipoR2 in mediating revascularization and metabolic dysfunction in vivo. J Biol Chem. 2014;289(23):16200–13. doi: 10.1074/jbc.M114.548115 24742672
54. Ton QV, Leino D, Mowery SA, Bredemeier NO, Lafontant PJ, Lubert A, et al. Collagen COL22A1 maintains vascular stability and mutations in COL22A1 are potentially associated with intracranial aneurysms. Dis Model Mech. 2018;11(12). doi: 10.1242/dmm.033654 30541770
55. Boskovski MT, Yuan S, Pedersen NB, Goth CK, Makova S, Clausen H, et al. The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality. Nature. 2013;504(7480):456–9. doi: 10.1038/nature12723 24226769
56. Li JP. Glucuronyl C5-epimerase an enzyme converting glucuronic acid to iduronic acid in heparan sulfate/heparin biosynthesis. Prog Mol Biol Transl Sci. 2010;93:59–78. doi: 10.1016/S1877-1173(10)93004-4 20807641.
57. Benard C, Tjoe N, Boulin T, Recio J, Hobert O. The small, secreted immunoglobulin protein ZIG-3 maintains axon position in Caenorhabditis elegans. Genetics. 2009;183(3):917–27. doi: 10.1534/genetics.109.107441 19737747
58. Gallegos ME, Bargmann CI. Mechanosensory neurite termination and tiling depend on SAX-2 and the SAX-1 kinase. Neuron. 2004;44(2):239–49. doi: 10.1016/j.neuron.2004.09.021 15473964.
59. Jia L, Emmons SW. Genes that control ray sensory neuron axon development in the Caenorhabditis elegans male. Genetics. 2006;173(3):1241–58. doi: 10.1534/genetics.106.057000 16624900
60. Simske JS, Koppen M, Sims P, Hodgkin J, Yonkof A, Hardin J. The cell junction protein VAB-9 regulates adhesion and epidermal morphology in C. elegans. Nat Cell Biol. 2003;5(7):619–25. doi: 10.1038/ncb1002 12819787.
61. Fisher SA, Rivera A, Fritsche LG, Keilhauer CN, Lichtner P, Meitinger T, et al. Case-control genetic association study of fibulin-6 (FBLN6 or HMCN1) variants in age-related macular degeneration (AMD). Hum Mutat. 2007;28(4):406–13. doi: 10.1002/humu.20464 17216616.
62. Parry DA, Mighell AJ, El-Sayed W, Shore RC, Jalili IK, Dollfus H, et al. Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta. Am J Hum Genet. 2009;84(2):266–73. doi: 10.1016/j.ajhg.2009.01.009 19200525
63. Polok B, Escher P, Ambresin A, Chouery E, Bolay S, Meunier I, et al. Mutations in CNNM4 cause recessive cone-rod dystrophy with amelogenesis imperfecta. Am J Hum Genet. 2009;84(2):259–65. doi: 10.1016/j.ajhg.2009.01.006 19200527
64. Al-Sayed MD, Al-Zaidan H, Albakheet A, Hakami H, Kenana R, Al-Yafee Y, et al. Mutations in NALCN cause an autosomal-recessive syndrome with severe hypotonia, speech impairment, and cognitive delay. Am J Hum Genet. 2013;93(4):721–6. doi: 10.1016/j.ajhg.2013.08.001 24075186
65. Ronchi D, Di Fonzo A, Lin W, Bordoni A, Liu C, Fassone E, et al. Mutations in DNA2 link progressive myopathy to mitochondrial DNA instability. Am J Hum Genet. 2013;92(2):293–300. doi: 10.1016/j.ajhg.2012.12.014 23352259
66. McKenna WL, Betancourt J, Larkin KA, Abrams B, Guo C, Rubenstein JL, et al. Tbr1 and Fezf2 regulate alternate corticofugal neuronal identities during neocortical development. J Neurosci. 2011;31(2):549–64. doi: 10.1523/JNEUROSCI.4131-10.2011 21228164
67. Suchi M, Mizuno H, Kawai Y, Tsuboi T, Sumi S, Okajima K, et al. Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families. Am J Hum Genet. 1997;60(3):525–39. 9042911
68. Molinari M, Calanca V, Galli C, Lucca P, Paganetti P. Role of EDEM in the release of misfolded glycoproteins from the calnexin cycle. Science. 2003;299(5611):1397–400. doi: 10.1126/science.1079474 12610306.
69. Smith AC, Mears AJ, Bunker R, Ahmed A, MacKenzie M, Schwartzentruber JA, et al. Mutations in the enzyme glutathione peroxidase 4 cause Sedaghatian-type spondylometaphyseal dysplasia. J Med Genet. 2014;51(7):470–4. doi: 10.1136/jmedgenet-2013-102218 24706940.
70. Rabin SJ, Kim JM, Baughn M, Libby RT, Kim YJ, Fan Y, et al. Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology. Hum Mol Genet. 2010;19(2):313–28. Epub 2009/10/30. doi: 10.1093/hmg/ddp498 19864493
71. Wu LS, Cheng WC, Chen CY, Wu MC, Wang YC, Tseng YH, et al. Transcriptomopathies of pre- and post-symptomatic frontotemporal dementia-like mice with TDP-43 depletion in forebrain neurons. Acta Neuropathol Commun. 2019;7(1):50. doi: 10.1186/s40478-019-0674-x 30922385
72. Stribl C, Samara A, Trumbach D, Peis R, Neumann M, Fuchs H, et al. Mitochondrial dysfunction and decrease in body weight of a transgenic knock-in mouse model for TDP-43. J Biol Chem. 2014;289(15):10769–84. doi: 10.1074/jbc.M113.515940 24515116
73. Blanchette CR, Thackeray A, Perrat PN, Hekimi S, Benard CY. Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans. PLoS Genet. 2017;13(1):e1006525. doi: 10.1371/journal.pgen.1006525 28068429
74. Bulow HE, Tjoe N, Townley RA, Didiano D, van Kuppevelt TH, Hobert O. Extracellular sugar modifications provide instructive and cell-specific information for axon-guidance choices. Curr Biol. 2008;18(24):1978–85. doi: 10.1016/j.cub.2008.11.023 19062279
75. Edwards TJ, Hammarlund M. Syndecan promotes axon regeneration by stabilizing growth cone migration. Cell Rep. 2014;8(1):272–83. doi: 10.1016/j.celrep.2014.06.008 25001284
76. Wang X, Liu J, Zhu Z, Ou G. The heparan sulfate-modifying enzyme glucuronyl C5-epimerase HSE-5 controls Caenorhabditis elegans Q neuroblast polarization during migration. Dev Biol. 2015;399(2):306–14. doi: 10.1016/j.ydbio.2015.01.007 25614236.
77. Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974;77:71–94. 4366476
78. Liachko NF, McMillan PJ, Guthrie CR, Bird TD, Leverenz JB, Kraemer BC. CDC7 inhibition blocks pathological TDP-43 phosphorylation and neurodegeneration. Ann Neurol. 2013. doi: 10.1002/ana.23870 23424178.
79. Kamath RS, Ahringer J. Genome-wide RNAi screening in Caenorhabditis elegans. Methods. 2003;30:313–21. doi: 10.1016/s1046-2023(03)00050-1 12828945
80. Liachko NF, Saxton AD, McMillan PJ, Strovas TJ, Currey HN, Taylor LM, et al. The phosphatase calcineurin regulates pathological TDP-43 phosphorylation. Acta Neuropathologica. 2016;132(4):545–61. doi: 10.1007/s00401-016-1600-y 27473149
81. Mackenzie IR, Neumann M, Baborie A, Sampathu DM, Du Plessis D, Jaros E, et al. A harmonized classification system for FTLD-TDP pathology. Acta Neuropathol. 2011;122(1):111–3. doi: 10.1007/s00401-011-0845-8 21644037
82. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–59. doi: 10.1007/bf00308809 1759558.
83. Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, et al. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology. 1991;41(4):479–86. doi: 10.1212/wnl.41.4.479 2011243.
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