Skip to main content
SpringerLink
Log in

Systems Biology of RNA-Binding Proteins in Amyotrophic Lateral Sclerosis

  • Chapter
  • First Online:
Book cover Systems Biology

Part of the book series: RNA Technologies ((RNATECHN))

  • 1635 Accesses

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult-onset incurable neurodegenerative disease. Although the precise pathogenesis of ALS remains unknown, mutations in genes encoding RNA-binding proteins (RBPs) have been known as a major culprit. RBPs are involved in almost every aspect of RNA metabolism events from synthesis to degradation. Characteristic features of RBPs in neurodegeneration include misregulation of RNA processing, mislocalization of RBPs to the cytoplasm, and unusual aggregation of RBPs. Modern advancement in technology and computational capabilities suggests an optimistic future for deconvolution of the pathological changes associated with ALS to identify the pathomechanisms of ALS. Importantly, combination of highly multidimensional omic technologies involving proteomics, microarray, and mass spectrometry with computational systems biology approaches provides a systemic methodology to reveal novel mechanisms behind ALS. In this chapter, we begin by summarizing the ALS and involvement of RBPs in ALS. Further, we provide a comprehensive overview of applications of systems biology to study ALS. We imagine that the integration of highly efficient computational tools with multiple omic analyses will help in the discovery of new therapeutic interventions in ALS.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Anderson P, Kedersha N (2009) RNA granules: post-transcriptional and epigenetic modulators of gene expression. Nat Rev Mol Cell Biol 10:430–436

    Article  PubMed  CAS  Google Scholar 

  • Appel SH, Rowland LP (2012) Amyotrophic lateral sclerosis, frontotemporal lobar dementia, and p62: a functional convergence? Neurology 79:1526–1527

    Article  PubMed  Google Scholar 

  • Arai T, Hasegawa M, Akiyama H et al (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351:602–611

    Article  PubMed  CAS  Google Scholar 

  • Aulas A, Vande Velde C (2015) Alterations in stress granule dynamics driven by TDP-43 and FUS: a link to pathological inclusions in ALS? Front Cell Neurosci 9:423

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Belzil VV, Gendron TF, Petrucelli L (2013) RNA-mediated toxicity in neurodegenerative disease. Mol Cell Neurosci 56:406–419

    Article  PubMed  CAS  Google Scholar 

  • Bentmann E, Haass C, Dormann D (2013) Stress granules in neurodegeneration—lessons learnt from TAR DNA binding protein of 43 kDa and fused in sarcoma. FEBS J 280:4348–4370

    Article  PubMed  CAS  Google Scholar 

  • Blasco H, Corcia P, Moreau C et al (2010) 1H-NMR-based metabolomic profiling of CSF in early amyotrophic lateral sclerosis. PLoS One 5:e13223

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Boillee S, Yamanaka K, Lobsiger CS et al (2006) Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312:1389–1392

    Article  PubMed  CAS  Google Scholar 

  • Boutahar N, Wierinckx A, Camdessanche JP et al (2011) Differential effect of oxidative or excitotoxic stress on the transcriptional profile of amyotrophic lateral sclerosis-linked mutant SOD1 cultured neurons. J Neurosci Res 89:1439–1450

    Article  PubMed  CAS  Google Scholar 

  • Bucchia M, Ramirez A, Parente V et al (2015) Therapeutic development in amyotrophic lateral sclerosis. Clin Ther 37:668–680

    Article  PubMed  Google Scholar 

  • Buchan JR (2014) mRNP granules. Assembly, function, and connections with disease. RNA Biol 11:1019–1030

    Article  PubMed  PubMed Central  Google Scholar 

  • Burrell JR, Kiernan MC, Vucic S et al (2011) Motor neuron dysfunction in frontotemporal dementia. Brain 134:2582–2594

    Article  PubMed  Google Scholar 

  • Caballero-Hernandez D, Toscano MG, Cejudo-Guillen M et al (2016) The ‘Omics’ of amyotrophic lateral sclerosis. Trends Mol Med 22:53–67

    Article  PubMed  CAS  Google Scholar 

  • Cistaro A, Pagani M, Montuschi A et al (2014) The metabolic signature of C9ORF72-related ALS: FDG PET comparison with nonmutated patients. Eur J Nucl Med Mol Imaging 41:844–852

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Conlon EG, Lu L, Sharma A et al (2016) The C9ORF72 GGGGCC expansion forms RNA G-quadruplex inclusions and sequesters hnRNP H to disrupt splicing in ALS brains. Elife 5:e17820

    Article  PubMed  PubMed Central  Google Scholar 

  • Cooper-Knock J, Walsh MJ, Higginbottom A et al (2014) Sequestration of multiple RNA recognition motif-containing proteins by C9orf72 repeat expansions. Brain 137:2040–2051

    Article  PubMed  PubMed Central  Google Scholar 

  • Cooper-Knock J, Bury JJ, Heath PR et al (2015) C9ORF72 GGGGCC expanded repeats produce splicing dysregulation which correlates with disease severity in amyotrophic lateral sclerosis. PLoS One 10:e0127376

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Coyne AN, Zaepfel BL, Zarnescu DC (2017) Failure to deliver and translate-new insights into RNA dysregulation in ALS. Front Cell Neurosci 11:243

    Article  PubMed  PubMed Central  Google Scholar 

  • Cwik VA, Hanstock CC, Allen PS et al (1998) Estimation of brainstem neuronal loss in amyotrophic lateral sclerosis with in vivo proton magnetic resonance spectroscopy. Neurology 50:72–77

    Article  PubMed  CAS  Google Scholar 

  • Daigle JG, Lanson NA Jr, Smith RB et al (2013) RNA-binding ability of FUS regulates neurodegeneration, cytoplasmic mislocalization and incorporation into stress granules associated with FUS carrying ALS-linked mutations. Hum Mol Genet 22:1193–1205

    Article  PubMed  CAS  Google Scholar 

  • DeJesus-Hernandez M, Mackenzie IR, Boeve BF et al (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72:245–256

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • DeLoach A, Cozart M, Kiaei A et al (2015) A retrospective review of the progress in amyotrophic lateral sclerosis drug discovery over the last decade and a look at the latest strategies. Expert Opin Drug Discov 10:1099–1118

    Article  PubMed  CAS  Google Scholar 

  • Deng HX, Chen W, Hong ST et al (2011) Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature 477:211–215

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dewey CM, Cenik B, Sephton CF et al (2012) TDP-43 aggregation in neurodegeneration: are stress granules the key? Brain Res 1462:16–25

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Diaz-Beltran L, Cano C, Wall DP et al (2013) Systems biology as a comparative approach to understand complex gene expression in neurological diseases. Behav Sci (Basel) 3:253–272

    Article  Google Scholar 

  • Dowling P, Clynes M (2011) Conditioned media from cell lines: a complementary model to clinical specimens for the discovery of disease-specific biomarkers. Proteomics 11:794–804

    Article  PubMed  CAS  Google Scholar 

  • Dunkel P, Chai CL, Sperlagh B et al (2012) Clinical utility of neuroprotective agents in neurodegenerative diseases: current status of drug development for Alzheimer’s, Parkinson’s and Huntington’s diseases, and amyotrophic lateral sclerosis. Expert Opin Investig Drugs 21:1267–1308

    Article  PubMed  CAS  Google Scholar 

  • Figueroa-Romero C, Hur J, Bender DE et al (2012) Identification of epigenetically altered genes in sporadic amyotrophic lateral sclerosis. PLoS One 7:e52672

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Freischmidt A, Wieland T, Richter B et al (2015) Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. Nat Neurosci 18:631–636

    Article  PubMed  CAS  Google Scholar 

  • Fujioka Y, Ishigaki S, Masuda A et al (2013) FUS-regulated region- and cell-type-specific transcriptome is associated with cell selectivity in ALS/FTLD. Sci Rep 3:2388

    Article  PubMed  PubMed Central  Google Scholar 

  • Gendron TF, Petrucelli L (2017) Disease mechanisms of C9ORF72 repeat expansions. Cold Spring Harb Perspect Med 8:a024224

    Article  Google Scholar 

  • Gendron TF, Belzil VV, Zhang YJ et al (2014) Mechanisms of toxicity in C9FTLD/ALS. Acta Neuropathol 127:359–376

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gomes C, Escrevente C, Costa J (2010) Mutant superoxide dismutase 1 overexpression in NSC-34 cells: effect of trehalose on aggregation, TDP-43 localization and levels of co-expressed glycoproteins. Neurosci Lett 475:145–149

    Article  PubMed  CAS  Google Scholar 

  • Goyal NA, Mozaffar T (2014) Experimental trials in amyotrophic lateral sclerosis: a review of recently completed, ongoing and planned trials using existing and novel drugs. Expert Opin Investig Drugs 23:1541–1551

    Article  PubMed  CAS  Google Scholar 

  • Grad LI, Pokrishevsky E, Silverman JM et al (2014) Exosome-dependent and independent mechanisms are involved in prion-like transmission of propagated Cu/Zn superoxide dismutase misfolding. Prion 8:331–335

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gredal O, Rosenbaum S, Topp S et al (1997) Quantification of brain metabolites in amyotrophic lateral sclerosis by localized proton magnetic resonance spectroscopy. Neurology 48:878–881

    Article  PubMed  CAS  Google Scholar 

  • Haeusler AR, Donnelly CJ, Periz G et al (2014) C9orf72 nucleotide repeat structures initiate molecular cascades of disease. Nature 507:195–200

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Haidet-Phillips AM, Hester ME, Miranda CJ et al (2011) Astrocytes from familial and sporadic ALS patients are toxic to motor neurons. Nat Biotechnol 29:824–828

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hazelett DJ, Chang JC, Lakeland DL et al (2012) Comparison of parallel high-throughput RNA sequencing between knockout of TDP-43 and its overexpression reveals primarily nonreciprocal and nonoverlapping gene expression changes in the central nervous system of Drosophila. G3 (Bethesda) 2:789–802

    Article  PubMed Central  CAS  Google Scholar 

  • He Y, Smith R (2009) Nuclear functions of heterogeneous nuclear ribonucleoproteins A/B. Cell Mol Life Sci 66:1239–1256

    Article  PubMed  CAS  Google Scholar 

  • Heath PR, Kirby J, Shaw PJ (2013) Investigating cell death mechanisms in amyotrophic lateral sclerosis using transcriptomics. Front Cell Neurosci 7:259

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Heck MV, Azizov M, Stehning T et al (2014) Dysregulated expression of lipid storage and membrane dynamics factors in Tia1 knockout mouse nervous tissue. Neurogenetics 15:135–144

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Henriques A, Gonzalez De Aguilar JL (2011) Can transcriptomics cut the gordian knot of amyotrophic lateral sclerosis? Curr Genomics 12:506–515

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hicks GG, Singh N, Nashabi A et al (2000) Fus deficiency in mice results in defective B-lymphocyte development and activation, high levels of chromosomal instability and perinatal death. Nat Genet 24:175–179

    Article  PubMed  CAS  Google Scholar 

  • Highley JR, Kirby J, Jansweijer JA et al (2014) Loss of nuclear TDP-43 in amyotrophic lateral sclerosis (ALS) causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurones. Neuropathol Appl Neurobiol 40:670–685

    Article  PubMed  CAS  Google Scholar 

  • Honda D, Ishigaki S, Iguchi Y et al (2013) The ALS/FTLD-related RNA-binding proteins TDP-43 and FUS have common downstream RNA targets in cortical neurons. FEBS Open Bio 4:1–10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ikeda K, Iwasaki Y, Kinoshita M et al (1998) Quantification of brain metabolites in ALS by localized proton magnetic spectroscopy. Neurology 50:576–577

    Article  PubMed  CAS  Google Scholar 

  • Ilieva H, Polymenidou M, Cleveland DW (2009) Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond. J Cell Biol 187:761–772

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jones AP, Gunawardena WJ, Coutinho CM et al (1995) Preliminary results of proton magnetic resonance spectroscopy in motor neurone disease (amyotrophic lateral sclerosis). J Neurol Sci 129(Suppl):85–89

    Article  PubMed  Google Scholar 

  • Kabashi E, Valdmanis PN, Dion P et al (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 40:572–574

    Article  PubMed  CAS  Google Scholar 

  • Kapeli K, Martinez FJ, Yeo GW (2017) Genetic mutations in RNA-binding proteins and their roles in ALS. Hum Genet 136:1193–1214

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kim HJ, Kim NC, Wang YD et al (2013) Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 495:467–473

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kraemer BC, Schuck T, Wheeler JM et al (2010) Loss of murine TDP-43 disrupts motor function and plays an essential role in embryogenesis. Acta Neuropathol 119:409–419

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Krokidis MG, Vlamos P (2018) Transcriptomics in amyotrophic lateral sclerosis. Front Biosci (Elite Ed) 10:103–121

    Article  Google Scholar 

  • Kumar V, Islam A, Hassan MI et al (2016a) Therapeutic progress in amyotrophic lateral sclerosis-beginning to learning. Eur J Med Chem 121:903–917

    Article  PubMed  CAS  Google Scholar 

  • Kumar V, Islam A, Hassan MI et al (2016b) Delineating the relationship between amyotrophic lateral sclerosis and frontotemporal dementia: sequence and structure-based predictions. Biochim Biophys Acta 1862:1742–1754

    Article  PubMed  CAS  Google Scholar 

  • Kumar V, Kashav T, Islam A et al (2016c) Structural insight into C9orf72 hexanucleotide repeat expansions: towards new therapeutic targets in FTD-ALS. Neurochem Int 100:11–20

    Article  PubMed  CAS  Google Scholar 

  • Kwiatkowski TJ Jr, Bosco DA, Leclerc AL et al (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323:1205–1208

    Article  PubMed  CAS  Google Scholar 

  • Lawton KA, Cudkowicz ME, Brown MV et al (2012) Biochemical alterations associated with ALS. Amyotroph Lateral Scler 13:110–118

    Article  PubMed  CAS  Google Scholar 

  • Lawton KA, Brown MV, Alexander D et al (2014) Plasma metabolomic biomarker panel to distinguish patients with amyotrophic lateral sclerosis from disease mimics. Amyotroph Lateral Scler Frontotemporal Degener 15:362–370

    Article  PubMed  CAS  Google Scholar 

  • Lee KH, Zhang P, Kim HJ et al (2016) C9orf72 dipeptide repeats impair the assembly, dynamics, and function of membrane-less organelles. Cell 167:774–788.e717

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee YB, Chen HJ, Peres JN et al (2013) Hexanucleotide repeats in ALS/FTD form length-dependent RNA foci, sequester RNA binding proteins, and are neurotoxic. Cell Rep 5:1178–1186

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li H, Watford W, Li C et al (2007) Ewing sarcoma gene EWS is essential for meiosis and B lymphocyte development. J Clin Invest 117:1314–1323

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ling SC, Polymenidou M, Cleveland DW (2013) Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron 79:416–438

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu TY, Chen YC, Jong YJ et al (2017) Muscle developmental defects in heterogeneous nuclear Ribonucleoprotein A1 knockout mice. Open Biol 7:160303

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lomen-Hoerth C, Anderson T, Miller B (2002) The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 59:1077–1079

    Article  PubMed  Google Scholar 

  • Maharjan N, Kunzli C, Buthey K et al (2017) C9ORF72 regulates stress granule formation and its deficiency impairs stress granule assembly, hypersensitizing cells to stress. Mol Neurobiol 54:3062–3077

    Article  PubMed  CAS  Google Scholar 

  • Mancuso R, Navarro X (2015) Amyotrophic lateral sclerosis: current perspectives from basic research to the clinic. Prog Neurobiol 133:1–26

    Article  PubMed  Google Scholar 

  • Mehta P, Kaye W, Bryan L et al (2016) Prevalence of amyotrophic lateral sclerosis – United States, 2012–2013. MMWR Surveill Summ 65:1–12

    Article  PubMed  Google Scholar 

  • Mori K, Lammich S, Mackenzie IR et al (2013) hnRNP A3 binds to GGGGCC repeats and is a constituent of p62-positive/TDP43-negative inclusions in the hippocampus of patients with C9orf72 mutations. Acta Neuropathol 125:413–423

    Article  PubMed  CAS  Google Scholar 

  • Morozova O, Marra MA (2008) Applications of next-generation sequencing technologies in functional genomics. Genomics 92:255–264

    Article  PubMed  CAS  Google Scholar 

  • Moujalled D, White AR (2016) Advances in the development of disease-modifying treatments for amyotrophic lateral sclerosis. CNS Drugs 30:227–243

    Article  PubMed  CAS  Google Scholar 

  • Nakaya T, Alexiou P, Maragkakis M et al (2013) FUS regulates genes coding for RNA-binding proteins in neurons by binding to their highly conserved introns. RNA 19:498–509

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Narayanan RK, Mangelsdorf M, Panwar A et al (2013) Identification of RNA bound to the TDP-43 ribonucleoprotein complex in the adult mouse brain. Amyotroph Lateral Scler Frontotemporal Degener 14:252–260

    Article  PubMed  CAS  Google Scholar 

  • Nicholson KA, Cudkowicz ME, Berry JD (2015) Clinical trial designs in amyotrophic lateral sclerosis: does one design fit all? Neurotherapeutics 12:376–383

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nussbacher JK, Batra R, Lagier-Tourenne C et al (2015) RNA-binding proteins in neurodegeneration: Seq and you shall receive. Trends Neurosci 38:226–236

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pandya RS, Zhu H, Li W et al (2013) Therapeutic neuroprotective agents for amyotrophic lateral sclerosis. Cell Mol Life Sci 70:4729–4745

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Paratore S, Pezzino S, Cavallaro S (2012) Identification of pharmacological targets in amyotrophic lateral sclerosis through genomic analysis of deregulated genes and pathways. Curr Genomics 13:321–333

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Perry DC, Miller BL (2013) Frontotemporal dementia. Semin Neurol 33:336–341

    Article  PubMed  Google Scholar 

  • Polymenidou M, Lagier-Tourenne C, Hutt KR et al (2012) Misregulated RNA processing in amyotrophic lateral sclerosis. Brain Res 1462:3–15

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Protter DS, Parker R (2016) Principles and properties of stress granules. Trends Cell Biol 26:668–679

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Prudencio M, Belzil VV, Batra R et al (2015) Distinct brain transcriptome profiles in C9orf72-associated and sporadic ALS. Nat Neurosci 18:1175–1182

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ramaswami M, Taylor JP, Parker R (2013) Altered ribostasis: RNA-protein granules in degenerative disorders. Cell 154:727–736

    Article  PubMed  CAS  Google Scholar 

  • Ratnavalli E, Brayne C, Dawson K et al (2002) The prevalence of frontotemporal dementia. Neurology 58:1615–1621

    Article  PubMed  CAS  Google Scholar 

  • Reis-Filho JS (2009) Next-generation sequencing. Breast Cancer Res 11(Suppl 3):S12

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Renton AE, Majounie E, Waite A et al (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72:257–268

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ringholz GM, Appel SH, Bradshaw M et al (2005) Prevalence and patterns of cognitive impairment in sporadic ALS. Neurology 65:586–590

    Article  PubMed  CAS  Google Scholar 

  • Robberecht W, Philips T (2013) The changing scene of amyotrophic lateral sclerosis. Nat Rev Neurosci 14:248–264

    Article  PubMed  CAS  Google Scholar 

  • Rosen DR, Siddique T, Patterson D et al (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62

    Article  PubMed  CAS  Google Scholar 

  • Rossi S, Serrano A, Gerbino V et al (2015) Nuclear accumulation of mRNAs underlies G4C2-repeat-induced translational repression in a cellular model of C9orf72 ALS. J Cell Sci 128:1787–1799

    Article  PubMed  CAS  Google Scholar 

  • Rozen S, Cudkowicz ME, Bogdanov M et al (2005) Metabolomic analysis and signatures in motor neuron disease. Metabolomics 1:101–108

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sareen D, O’Rourke JG, Meera P et al (2013) Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9ORF72 repeat expansion. Sci Transl Med 5:208ra149

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Saris CG, Groen EJ, Koekkoek JA et al (2013a) Meta-analysis of gene expression profiling in amyotrophic lateral sclerosis: a comparison between transgenic mouse models and human patients. Amyotroph Lateral Scler Frontotemporal Degener 14:177–189

    Article  PubMed  CAS  Google Scholar 

  • Saris CG, Groen EJ, van Vught PW et al (2013b) Gene expression profile of SOD1-G93A mouse spinal cord, blood and muscle. Amyotroph Lateral Scler Frontotemporal Degener 14:190–198

    Article  PubMed  CAS  Google Scholar 

  • Satoh J, Yamamoto Y, Kitano S et al (2014) Molecular network analysis suggests a logical hypothesis for the pathological role of c9orf72 in amyotrophic lateral sclerosis/frontotemporal dementia. J Cent Nerv Syst Dis 6:69–78

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shaw PJ (2005) Molecular and cellular pathways of neurodegeneration in motor neurone disease. J Neurol Neurosurg Psychiatry 76:1046–1057

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sieben A, Van Langenhove T, Engelborghs S et al (2012) The genetics and neuropathology of frontotemporal lobar degeneration. Acta Neuropathol 124:353–372

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sreedharan J, Blair IP, Tripathi VB et al (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319:1668–1672

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stepto A, Gallo JM, Shaw CE et al (2014) Modelling C9ORF72 hexanucleotide repeat expansion in amyotrophic lateral sclerosis and frontotemporal dementia. Acta Neuropathol 127:377–389

    Article  PubMed  CAS  Google Scholar 

  • Todd TW, Petrucelli L (2016) Insights into the pathogenic mechanisms of Chromosome 9 open reading frame 72 (C9orf72) repeat expansions. J Neurochem 138:145–162

    Article  PubMed  CAS  Google Scholar 

  • Urushitani M, Sik A, Sakurai T et al (2006) Chromogranin-mediated secretion of mutant superoxide dismutase proteins linked to amyotrophic lateral sclerosis. Nat Neurosci 9:108–118

    Article  PubMed  CAS  Google Scholar 

  • van Blitterswijk M, van Es MA, Hennekam EA et al (2012) Evidence for an oligogenic basis of amyotrophic lateral sclerosis. Hum Mol Genet 21:3776–3784

    Article  PubMed  CAS  Google Scholar 

  • van Blitterswijk M, Wang ET, Friedman BA et al (2013) Characterization of FUS mutations in amyotrophic lateral sclerosis using RNA-Seq. PLoS One 8:e60788

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang B, Xi Y (2013) Challenges for microRNA microarray data analysis. Microarrays (Basel) 2:34–50

    Article  CAS  Google Scholar 

  • Wen X, Westergard T, Pasinelli P et al (2017) Pathogenic determinants and mechanisms of ALS/FTD linked to hexanucleotide repeat expansions in the C9orf72 gene. Neurosci Lett 636:16–26

    Article  PubMed  CAS  Google Scholar 

  • Wheaton MW, Salamone AR, Mosnik DM et al (2007) Cognitive impairment in familial ALS. Neurology 69:1411–1417

    Article  PubMed  CAS  Google Scholar 

  • Wood LB, Winslow AR, Strasser SD (2015) Systems biology of neurodegenerative diseases. Integr Biol (Camb) 7:758–775

    Article  CAS  Google Scholar 

  • Wroe R, Wai-Ling Butler A, Andersen PM et al (2008) ALSOD: the amyotrophic lateral sclerosis online database. Amyotroph Lateral Scler 9:249–250

    Article  PubMed  CAS  Google Scholar 

  • Wu CH, Fallini C, Ticozzi N et al (2012) Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 488:499–503

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wuolikainen A, Hedenstrom M, Moritz T et al (2009) Optimization of procedures for collecting and storing of CSF for studying the metabolome in ALS. Amyotroph Lateral Scler 10:229–236

    Article  PubMed  Google Scholar 

  • Wuolikainen A, Moritz T, Marklund SL et al (2011) Disease-related changes in the cerebrospinal fluid metabolome in amyotrophic lateral sclerosis detected by GC/TOFMS. PLoS One 6:e17947

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhan L, Hanson KA, Kim SH et al (2013) Identification of genetic modifiers of TDP-43 neurotoxicity in Drosophila. PLoS One 8:e57214

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgement

TK thanks the Department of Biotechnology, India, for providing DBT Biocare fellowship (BT/Bio-CARe/07/351/2016–2018). VK thanks the Department of Science of Technology, India, for the award of DST fast track fellowship (SB/YS/LS-161/2014).

Conflict of Interest The authors have declared that there is no conflict of interest.

Author information

Authors and Affiliations

  1. Centre for Biological Sciences, Central University of South Bihar, Patna, India

    Tara Kashav

  2. Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India

    Vijay Kumar

Authors
  1. Tara Kashav
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vijay Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vijay Kumar .

Editor information

Editors and Affiliations

  1. Max Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, Berlin-Buch, Berlin, Germany

    Nikolaus Rajewsky

  2. Nanobiomedical Center, Adam Mickiewicz University, Poznań, Poland

    Stefan Jurga

  3. Polish Academy of Sciences, Institute of Bioorganic Chemistry, Poznań, Poland

    Jan Barciszewski

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kashav, T., Kumar, V. (2018). Systems Biology of RNA-Binding Proteins in Amyotrophic Lateral Sclerosis. In: Rajewsky, N., Jurga, S., Barciszewski, J. (eds) Systems Biology. RNA Technologies. Springer, Cham. https://doi.org/10.1007/978-3-319-92967-5_4

Download citation

Publish with us

Policies and ethics

Search

Navigation