Skip to main content
SpringerLink
Log in

Conformational Disease and RNA Disease Theory in the Context of Neurodegenerative Diseases

  • Chapter
Neurodegenerative Disorders as Systemic Diseases

  • 847 Accesses

Abstract

Neurodegenerative diseases cause slowly progressive loss of specific systems of the nervous tissues and show unique neuronal inclusions. During the last 30 years, the causative genes of many hereditary neurodegenerative diseases and the components of most of their characteristic inclusions have been identified. However, the molecular mechanisms responsible for neuronal degeneration have not been fully clarified. Here we review the history of neurodegenerative disorders and current explanations for their molecular pathogenesis – conformational disease theory and RNA disease theory – which attempt to explain the vulnerability of neurons to these disorders in terms of their unique cell features.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

  • Alzheimer A (1911) Über eigenartige Krankheitsfälle des späteren Alters. Zeitschrift für die gesamte Neurologie und Psychiatrie 4:356–385

    Article  Google Scholar 

  • Anderson P, Kedersha N (2008) Stress granules: the Tao of RNA triage. Trends Biochem Sci 33:141–150

    Article  CAS  PubMed  Google Scholar 

  • Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H, Mann D, Tsuchiya K, Yoshida M, Hashizume Y, Oda T (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  CAS  PubMed  Google Scholar 

  • Aulas A, Stabile S, Vande VC (2012) Endogenous TDP-43, but not FUS, contributes to stress granule assembly via G3BP. Mol Neurodegener 7:54

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Austin JA, Wright GS, Watanabe S, Grossmann JG, Antonyuk SV, Yamanaka K, Hasnain SS (2014) Disease causing mutants of TDP-43 nucleic acid binding domains are resistant to aggregation and have increased stability and half-life. Proc Natl Acad Sci U S A 111:4309–4314

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Barghorn S, Davies P, Mandelkow E (2004) Tau paired helical filaments from Alzheimer’s disease brain and assembled in vitro are based on beta-structure in the core domain. Biochemistry 43:1694–1703

    Article  CAS  PubMed  Google Scholar 

  • Bendheim PE, Brown HR, Rudelli RD, Scala LJ, Goller NL, Wen GY, Kascsak RJ, Cashman NR, Bolton DC (1992) Nearly ubiquitous tissue distribution of the scrapie agent precursor protein. Neurology 42:149–156

    Article  CAS  PubMed  Google Scholar 

  • Borroni B, Bonvicini C, Alberici A, Buratti E, Agosti C, Archetti S, Papetti A, Stuani C, Di Luca M, Gennarelli M (2009) Mutation within TARDBP leads to frontotemporal dementia without motor neuron disease. Hum Mutat 30:E974–E983

    Article  CAS  PubMed  Google Scholar 

  • Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211

    Article  PubMed  Google Scholar 

  • Brown P, Brandel JP, Sato T, Nakamura Y, MacKenzie J, Will RG, Ladogana A, Pocchiari M, Leschek EW, Schonberger LB (2012) Iatrogenic Creutzfeldt-Jakob disease, final assessment. Emerg Infect Dis 18:901–907

    Article  PubMed Central  PubMed  Google Scholar 

  • Brundin P, Melki R, Kopito R (2010) Prion-like transmission of protein aggregates in neurodegenerative diseases. Nat Rev Mol Cell Biol 11:301–307

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Burghes AH, Beattie CE (2009) Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick? Nat Rev Neurosci 10:597–609

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Burlet P, Huber C, Bertrandy S, Ludosky MA, Zwaenepoel I, Clermont O, Roume J, Delezoide AL, Cartaud J, Munnich A, Lefebvre S (1998) The distribution of SMN protein complex in human fetal tissues and its alteration in spinal muscular atrophy. Hum Mol Genet 7:1927–1933

    Article  CAS  PubMed  Google Scholar 

  • Carrell RW, Lomas DA (1997) Conformational disease. Lancet 350:134–138

    Article  CAS  PubMed  Google Scholar 

  • Chai Y, Koppenhafer SL, Shoesmith SJ, Perez MK, Paulson HL (1999) Evidence for proteasome involvement in polyglutamine disease: localization to nuclear inclusions in SCA3/MJD and suppression of polyglutamine aggregation in vitro. Hum Mol Genet 8:673–682

    Article  CAS  PubMed  Google Scholar 

  • Charcot J-M, Joffroy A (1869) Deux cas d’atrophie musculaire progressive: avec lésions de la substance grise et des faisceaux antérolatéraux de la moelle épinière. Masson, Paris

    Google Scholar 

  • Chare L, Hodges JR, Leyton CE, McGinley C, Tan RH, Kril JJ, Halliday GM (2014) New criteria for frontotemporal dementia syndromes: clinical and pathological diagnostic implications. J Neurol Neurosurg Psychiatry 85:866–871

    Google Scholar 

  • Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, Fraser G, Stalder AK, Beibel M, Staufenbiel M, Jucker M, Goedert M, Tolnay M (2009) Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol 11:909–913

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cleary JD, Ranum LP (2013) Repeat-associated non-ATG (RAN) translation in neurological disease. Hum Mol Genet 22:R45–R51

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Coady TH, Lorson CL (2011) SMN in spinal muscular atrophy and snRNP biogenesis. Wiley Interdiscip Rev RNA 2:546–564

    Article  CAS  PubMed  Google Scholar 

  • Cohen FE, Pan KM, Huang Z, Baldwin M, Fletterick RJ, Prusiner SB (1994) Structural clues to prion replication. Science 264:530–531

    Article  CAS  PubMed  Google Scholar 

  • Cooper TA, Wan L, Dreyfuss G (2009) RNA and disease. Cell 136:777–793

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Couthouis J, Hart MP, Shorter J, DeJesus-Hernandez M, Erion R, Oristano R, Liu AX, Ramos D, Jethava N, Hosangadi D, Epstein J, Chiang A, Diaz Z, Nakaya T, Ibrahim F, Kim HJ, Solski JA, Williams KL, Mojsilovic-Petrovic J, Ingre C, Boylan K, Graff-Radford NR, Dickson DW, Clay-Falcone D, Elman L, McCluskey L, Greene R, Kalb RG, Lee VM, Trojanowski JQ, Ludolph A, Robberecht W, Andersen PM, Nicholson GA, Blair IP, King OD, Bonini NM, Van Deerlin V, Rademakers R, Mourelatos Z, Gitler AD (2011) A yeast functional screen predicts new candidate ALS disease genes. Proc Natl Acad Sci U S A 108:20881–20890

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Couthouis J, Hart MP, Erion R, King OD, Diaz Z, Nakaya T, Ibrahim F, Kim HJ, Mojsilovic-Petrovic J, Panossian S, Kim CE, Frackelton EC, Solski JA, Williams KL, Clay-Falcone D, Elman L, McCluskey L, Greene R, Hakonarson H, Kalb RG, Lee VM, Trojanowski JQ, Nicholson GA, Blair IP, Bonini NM, Van Deerlin VM, Mourelatos Z, Shorter J, Gitler AD (2012) Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis. Hum Mol Genet 21:2899–2911

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Crouch PJ, Savva MS, Hung LW, Donnelly PS, Mot AI, Parker SJ, Greenough MA, Volitakis I, Adlard PA, Cherny RA, Masters CL, Bush AI, Barnham KJ, White AR (2011) The Alzheimer’s therapeutic PBT2 promotes amyloid-beta degradation and GSK3 phosphorylation via a metal chaperone activity. J Neurochem 119:220–230

    Article  CAS  PubMed  Google Scholar 

  • Davtyan H, Ghochikyan A, Petrushina I, Hovakimyan A, Davtyan A, Poghosyan A, Marleau AM, Movsesyan N, Kiyatkin A, Rasool S, Larsen AK, Madsen PJ, Wegener KM, Ditlevsen DK, Cribbs DH, Pedersen LO, Agadjanyan MG (2013) Immunogenicity, efficacy, safety, and mechanism of action of epitope vaccine (Lu AF20513) for Alzheimer’s disease: prelude to a clinical trial. J Neurosci Off J Soc Neurosci 33:4923–4934

    Article  CAS  Google Scholar 

  • de Leon MB, Cisneros B (2008) Myotonic dystrophy 1 in the nervous system: from the clinic to molecular mechanisms. J Neurosci Res 86:18–26

    Article  PubMed  CAS  Google Scholar 

  • DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NA, Flynn H, Adamson J, Kouri N, Wojtas A, Sengdy P, Hsiung GY, Karydas A, Seeley WW, Josephs KA, Coppola G, Geschwind DH, Wszolek ZK, Feldman H, Knopman DS, Petersen RC, Miller BL, Dickson DW, Boylan KB, Graff-Radford NR, Rademakers R (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72:245–256

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dormann D, Rodde R, Edbauer D, Bentmann E, Fischer I, Hruscha A, Than ME, Mackenzie IR, Capell A, Schmid B, Neumann M, Haass C (2010) ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. EMBO J 29:2841–2857

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dundr M (2012) Nuclear bodies: multifunctional companions of the genome. Curr Opin Cell Biol 24:415–422

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Elden AC, Kim HJ, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, Armakola M, Geser F, Greene R, Lu MM, Padmanabhan A, Clay-Falcone D, McCluskey L, Elman L, Juhr D, Gruber PJ, Rub U, Auburger G, Trojanowski JQ, Lee VM, Van Deerlin VM, Bonini NM, Gitler AD (2010) Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 466:1069–1075

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Eschbach J, Danzer KM (2014) Alpha-synuclein in Parkinson’s disease: pathogenic function and translation into animal models. Neuro-degener Dis 14:1–17

    Article  CAS  Google Scholar 

  • Farg MA, Soo KY, Warraich ST, Sundaramoorthy V, Blair IP, Atkin JD (2013) Ataxin-2 interacts with FUS and intermediate-length polyglutamine expansions enhance FUS-related pathology in amyotrophic lateral sclerosis. Hum Mol Genet 22:717–728

    Article  CAS  PubMed  Google Scholar 

  • Fevrier B, Vilette D, Archer F, Loew D, Faigle W, Vidal M, Laude H, Raposo G (2004) Cells release prions in association with exosomes. Proc Natl Acad Sci U S A 101:9683–9688

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Frost B, Diamond MI (2010) Prion-like mechanisms in neurodegenerative diseases. Nat Rev Neurosci 11:155–159

    PubMed Central  CAS  PubMed  Google Scholar 

  • Gabanella F, Butchbach ME, Saieva L, Carissimi C, Burghes AH, Pellizzoni L (2007) Ribonucleoprotein assembly defects correlate with spinal muscular atrophy severity and preferentially affect a subset of spliceosomal snRNPs. PLoS One 2:e921

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Gatchel JR, Zoghbi HY (2005) Diseases of unstable repeat expansion: mechanisms and common principles. Nat Rev Genet 6:743–755

    Article  CAS  PubMed  Google Scholar 

  • Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L et al (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349:704–706

    Article  CAS  PubMed  Google Scholar 

  • Goedert M, Spillantini MG (2006) A century of Alzheimer’s disease. Science 314:777–781

    Article  CAS  PubMed  Google Scholar 

  • Goedert M, Clavaguera F, Tolnay M (2010) The propagation of prion-like protein inclusions in neurodegenerative diseases. Trends Neurosci 33:317–325

    Article  CAS  PubMed  Google Scholar 

  • Gousset K, Schiff E, Langevin C, Marijanovic Z, Caputo A, Browman DT, Chenouard N, de Chaumont F, Martino A, Enninga J, Olivo-Marin JC, Mannel D, Zurzolo C (2009) Prions hijack tunnelling nanotubes for intercellular spread. Nat Cell Biol 11:328–336

    Article  CAS  PubMed  Google Scholar 

  • Guil S, Long JC, Caceres JF (2006) hnRNP A1 relocalization to the stress granules reflects a role in the stress response. Mol Cell Biol 26:5744–5758

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353–356

    Article  CAS  PubMed  Google Scholar 

  • Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, Hackett J, Adamson J, Lincoln S, Dickson D, Davies P, Petersen RC, Stevens M, de Graaff E, Wauters E, van Baren J, Hillebrand M, Joosse M, Kwon JM, Nowotny P, Che LK, Norton J, Morris JC, Reed LA, Trojanowski J, Basun H, Lannfelt L, Neystat M, Fahn S, Dark F, Tannenberg T, Dodd PR, Hayward N, Kwok JB, Schofield PR, Andreadis A, Snowden J, Craufurd D, Neary D, Owen F, Oostra BA, Hardy J, Goate A, van Swieten J, Mann D, Lynch T, Heutink P (1998) Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393:702–705

    Article  CAS  PubMed  Google Scholar 

  • Igarashi S, Tanno Y, Onodera O, Yamazaki M, Sato S, Ishikawa A, Miyatani N, Nagashima M, Ishikawa Y, Sahashi K et al (1992) Strong correlation between the number of CAG repeats in androgen receptor genes and the clinical onset of features of spinal and bulbar muscular atrophy. Neurology 42:2300–2302

    Article  CAS  PubMed  Google Scholar 

  • Iguchi Y, Katsuno M, Ikenaka K, Ishigaki S, Sobue G (2013) Amyotrophic lateral sclerosis: an update on recent genetic insights. J Neurol 260:2917–2927

    Article  CAS  PubMed  Google Scholar 

  • Iqbal K, Grundke-Iqbal I (2006) Discoveries of tau, abnormally hyperphosphorylated tau and others of neurofibrillary degeneration: a personal historical perspective. J Alzheimer’s Dis 9:219–242

    CAS  Google Scholar 

  • Irwin DJ, Abrams JY, Schonberger LB, Leschek EW, Mills JL, Lee VM, Trojanowski JQ (2013) Evaluation of potential infectivity of Alzheimer and Parkinson disease proteins in recipients of cadaver-derived human growth hormone. JAMA Neurol 70:462–468

    Article  PubMed Central  PubMed  Google Scholar 

  • Ishihara T, Ariizumi Y, Shiga A, Kato T, Tan CF, Sato T, Miki Y, Yokoo M, Fujino T, Koyama A, Yokoseki A, Nishizawa M, Kakita A, Takahashi H, Onodera O (2013) Decreased number of Gemini of coiled bodies and U12 snRNA level in amyotrophic lateral sclerosis. Hum Mol Genet 22:4136–4147

    Article  CAS  PubMed  Google Scholar 

  • Johnson BS, Snead D, Lee JJ, McCaffery JM, Shorter J, Gitler AD (2009) TDP-43 is intrinsically aggregation-prone, and amyotrophic lateral sclerosis-linked mutations accelerate aggregation and increase toxicity. J Biol Chem 284:20329–20339

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kiebler MA, Bassell GJ (2006) Neuronal RNA granules: movers and makers. Neuron 51:685–690

    Article  CAS  PubMed  Google Scholar 

  • Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JP (2013) Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 495:467–473

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • King OD, Gitler AD, Shorter J (2012) The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease. Brain Res 1462:61–80

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Konno T, Shiga A, Tsujino A, Sugai A, Kato T, Kanai K, Yokoseki A, Eguchi H, Kuwabara S, Nishizawa M, Takahashi H, Onodera O (2013) Japanese amyotrophic lateral sclerosis patients with GGGGCC hexanucleotide repeat expansion in C9ORF72. J Neurol Neurosurg Psychiatry 84:398–401

    Article  PubMed  Google Scholar 

  • Lagier-Tourenne C, Polymenidou M, Cleveland DW (2010) TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. Hum Mol Genet 19:R46–R64

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lansbury PT (1994) Mechanism of scrapie replication. Science 265:1510

    Article  CAS  PubMed  Google Scholar 

  • Lattante S, Rouleau GA, Kabashi E (2013) TARDBP and FUS mutations associated with amyotrophic lateral sclerosis: summary and update. Hum Mutat 34:812–826

    Article  CAS  PubMed  Google Scholar 

  • Lee JE, Cooper TA (2009) Pathogenic mechanisms of myotonic dystrophy. Biochem Soc Trans 37:1281–1286

    Article  CAS  PubMed  Google Scholar 

  • Lewy F (1912) Paralysis agitans. I. Pathologische anatomie. Handbuch der neurologie 3:920–933

    Google Scholar 

  • Li JY, Englund E, Holton JL, Soulet D, Hagell P, Lees AJ, Lashley T, Quinn NP, Rehncrona S, Bjorklund A, Widner H, Revesz T, Lindvall O, Brundin P (2008) Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat Med 14:501–503

    Article  CAS  PubMed  Google Scholar 

  • Li YR, King OD, Shorter J, Gitler AD (2013) Stress granules as crucibles of ALS pathogenesis. J Cell Biol 201:361–372

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Licatalosi DD, Darnell RB (2006) Splicing regulation in neurologic disease. Neuron 52:93–101

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lotti F, Imlach WL, Saieva L, Beck ES, le Hao T, Li DK, Jiao W, Mentis GZ, Beattie CE, McCabe BD, Pellizzoni L (2012) An SMN-dependent U12 splicing event essential for motor circuit function. Cell 151:440–454

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Luk KC, Kehm V, Carroll J, Zhang B, O’Brien P, Trojanowski JQ, Lee VM (2012) Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338:949–953

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mackenzie IR (2007) The neuropathology and clinical phenotype of FTD with progranulin mutations. Acta Neuropathol 114:49–54

    Article  PubMed  Google Scholar 

  • Manuelidis L, Chakrabarty T, Miyazawa K, Nduom NA, Emmerling K (2009) The kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt-Jakob disease and scrapie agents. Proc Natl Acad Sci U S A 106:13529–13534

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • McDonald KK, Aulas A, Destroismaisons L, Pickles S, Beleac E, Camu W, Rouleau GA, Vande VC (2011) TAR DNA-binding protein 43 (TDP-43) regulates stress granule dynamics via differential regulation of G3BP and TIA-1. Hum Mol Genet 20:1400–1410

    Article  CAS  PubMed  Google Scholar 

  • McMillan CT, Toledo JB, Avants BB, Cook PA, Wood EM, Suh E, Irwin DJ, Powers J, Olm C, Elman L, McCluskey L, Schellenberg GD, Lee VM, Trojanowski JQ, Van Deerlin VM, Grossman M (2014) Genetic and neuroanatomic associations in sporadic frontotemporal lobar degeneration. Neurobiol Aging 35:1473–1482

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Morris GE (2008) The Cajal body. Biochim Biophys Acta 1783:2108–2115

    Google Scholar 

  • Nagai Y, Inui T, Popiel HA, Fujikake N, Hasegawa K, Urade Y, Goto Y, Naiki H, Toda T (2007) A toxic monomeric conformer of the polyglutamine protein. Nat Struct Mol Biol 14:332–340

    Article  CAS  PubMed  Google Scholar 

  • Neuenkirchen N, Chari A, Fischer U (2008) Deciphering the assembly pathway of Sm-class U snRNPs. FEBS Lett 582:1997–2003

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Neumann M, Kwong LK, Sampathu DM, Trojanowski JQ, Lee VM (2007) TDP-43 proteinopathy in frontotemporal lobar degeneration and amyotrophic lateral sclerosis: protein misfolding diseases without amyloidosis. Arch Neurol 64:1388–1394

    Article  PubMed  Google Scholar 

  • Nevins TA, Harder ZM, Korneluk RG, Holcik M (2003) Distinct regulation of internal ribosome entry site-mediated translation following cellular stress is mediated by apoptotic fragments of eIF4G translation initiation factor family members eIF4GI and p97/DAP5/NAT1. J Biol Chem 278:3572–3579

    Article  CAS  PubMed  Google Scholar 

  • Nicoll JA, Wilkinson D, Holmes C, Steart P, Markham H, Weller RO (2003) Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med 9:448–452

    Article  CAS  PubMed  Google Scholar 

  • Nishihira Y, Tan CF, Onodera O, Toyoshima Y, Yamada M, Morita T, Nishizawa M, Kakita A, Takahashi H (2008) Sporadic amyotrophic lateral sclerosis: two pathological patterns shown by analysis of distribution of TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions. Acta Neuropathol 116:169–182

    Article  CAS  PubMed  Google Scholar 

  • O’Rourke JR, Swanson MS (2009) Mechanisms of RNA-mediated disease. J Biol Chem 284:7419–7423

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Orr HT, Zoghbi HY (2007) Trinucleotide repeat disorders. Annu Rev Neurosci 30:575–621

    Article  CAS  PubMed  Google Scholar 

  • Parchi P, Giese A, Capellari S, Brown P, Schulz-Schaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, Poser S, Rojiani A, Streichemberger N, Julien J, Vital C, Ghetti B, Gambetti P, Kretzschmar H (1999) Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 46:224–233

    Article  CAS  PubMed  Google Scholar 

  • Parkinson J (2002) An essay on the shaking palsy. 1817. J Neuropsychiatry Clin Neurosci 14:223–236, discussion 222

    Article  PubMed  Google Scholar 

  • Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276:2045–2047

    Article  CAS  PubMed  Google Scholar 

  • Prusiner SB (1998) The prion diseases. Brain Pathol 8:499–513

    Article  CAS  PubMed  Google Scholar 

  • Prusiner SB (2012) A unifying role for prions in neurodegenerative diseases. Science 336:1511–1513

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rademakers R, Cruts M, van Broeckhoven C (2004) The role of tau (MAPT) in frontotemporal dementia and related tauopathies. Hum Mutat 24:277–295

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EG, Onyike CU, Hillis AE, Josephs KA, Boeve BF, Kertesz A, Seeley WW, Rankin KP, Johnson JK, Gorno-Tempini ML, Rosen H, Prioleau-Latham CE, Lee A, Kipps CM, Lillo P, Piguet O, Rohrer JD, Rossor MN, Warren JD, Fox NC, Galasko D, Salmon DP, Black SE, Mesulam M, Weintraub S, Dickerson BC, Diehl-Schmid J, Pasquier F, Deramecourt V, Lebert F, Pijnenburg Y, Chow TW, Manes F, Grafman J, Cappa SF, Freedman M, Grossman M, Miller BL (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain J Neurol 134:2456–2477

    Article  Google Scholar 

  • Sawada H, Kohno R, Kihara T, Izumi Y, Sakka N, Ibi M, Nakanishi M, Nakamizo T, Yamakawa K, Shibasaki H, Yamamoto N, Akaike A, Inden M, Kitamura Y, Taniguchi T, Shimohama S (2004) Proteasome mediates dopaminergic neuronal degeneration, and its inhibition causes alpha-synuclein inclusions. J Biol Chem 279:10710–10719

    Article  CAS  PubMed  Google Scholar 

  • Sellier C, Rau F, Liu Y, Tassone F, Hukema RK, Gattoni R, Schneider A, Richard S, Willemsen R, Elliott DJ, Hagerman PJ, Charlet-Berguerand N (2010) Sam68 sequestration and partial loss of function are associated with splicing alterations in FXTAS patients. EMBO J 29:1248–1261

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shan X, Chiang PM, Price DL, Wong PC (2010) Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons of TDP-43 transgenic mice. Proc Natl Acad Sci U S A 107:16325–16330

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K (2003) Alpha-Synuclein locus triplication causes Parkinson’s disease. Science 302:841

    Article  CAS  PubMed  Google Scholar 

  • Spillantini MG, Goedert M (2013) Tau pathology and neurodegeneration. Lancet Neurol 12:609–622

    Article  CAS  PubMed  Google Scholar 

  • Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388:839–840

    Article  CAS  PubMed  Google Scholar 

  • Stokin GB, Lillo C, Falzone TL, Brusch RG, Rockenstein E, Mount SL, Raman R, Davies P, Masliah E, Williams DS, Goldstein LS (2005) Axonopathy and transport deficits early in the pathogenesis of Alzheimer’s disease. Science 307:1282–1288

    Article  CAS  PubMed  Google Scholar 

  • Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD (1993) Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A 90:1977–1981

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Takahashi T, Katada S, Onodera O (2010) Polyglutamine diseases: where does toxicity come from? what is toxicity? where are we going? J Mol Cell Biol 2:180–191

    Article  CAS  PubMed  Google Scholar 

  • Takeda A, Hasegawa T, Matsuzaki-Kobayashi M, Sugeno N, Kikuchi A, Itoyama Y, Furukawa K (2006) Mechanisms of neuronal death in synucleinopathy. J Biomed Biotechnol 2006:19365

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Takei N, Miyashita A, Tsukie T, Arai H, Asada T, Imagawa M, Shoji M, Higuchi S, Urakami K, Kimura H, Kakita A, Takahashi H, Tsuji S, Kanazawa I, Ihara Y, Odani S, Kuwano R, Japanese Genetic Study Consortium for Alzheimer D (2009) Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese. Genomics 93:441–448

    Article  CAS  PubMed  Google Scholar 

  • Todd PK, Paulson HL (2010) RNA-mediated neurodegeneration in repeat expansion disorders. Ann Neurol 67:291–300

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tomiyama T, Matsuyama S, Iso H, Umeda T, Takuma H, Ohnishi K, Ishibashi K, Teraoka R, Sakama N, Yamashita T, Nishitsuji K, Ito K, Shimada H, Lambert MP, Klein WL, Mori H (2010) A mouse model of amyloid beta oligomers: their contribution to synaptic alteration, abnormal tau phosphorylation, glial activation, and neuronal loss in vivo. J Neurosci Off J Soc Neurosci 30:4845–4856

    Article  CAS  Google Scholar 

  • Tsuiji H, Iguchi Y, Furuya A, Kataoka A, Hatsuta H, Atsuta N, Tanaka F, Hashizume Y, Akatsu H, Murayama S, Sobue G, Yamanaka K (2013) Spliceosome integrity is defective in the motor neuron diseases ALS and SMA. EMBO Mol Med 5:221–234

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tsuji S (2010) Genetics of neurodegenerative diseases: insights from high-throughput resequencing. Hum Mol Genet 19:R65–R70

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Turunen JJ, Niemela EH, Verma B, Frilander MJ (2013) The significant other: splicing by the minor spliceosome. Wiley Interdiscip Rev RNA 4:61–76

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, Ganesalingam J, Williams KL, Tripathi V, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo JM, Miller CC, Shaw CE (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323:1208–1211

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wakabayashi K, Matsumoto K, Takayama K, Yoshimoto M, Takahashi H (1997) NACP, a presynaptic protein, immunoreactivity in Lewy bodies in Parkinson’s disease. Neurosci Lett 239:45–48

    Article  CAS  PubMed  Google Scholar 

  • Wang IF, Reddy NM, Shen CK (2002) Higher order arrangement of the eukaryotic nuclear bodies. Proc Natl Acad Sci U S A 99:13583–13588

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW (1975) A protein factor essential for microtubule assembly. Proc Natl Acad Sci U S A 72:1858–1862

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Will CL, Luhrmann R (2005) Splicing of a rare class of introns by the U12-dependent spliceosome. Biol Chem 386:713–724

    Article  CAS  PubMed  Google Scholar 

  • Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A, Poser S, Pocchiari M, Hofman A, Smith PG (1996) A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 347:921–925

    Article  CAS  PubMed  Google Scholar 

  • Winklhofer KF, Tatzelt J, Haass C (2008) The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases. EMBO J 27:336–349

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wolozin B (2012) Regulated protein aggregation: stress granules and neurodegeneration. Mol Neurodegener 7:56

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yokoseki A, Shiga A, Tan CF, Tagawa A, Kaneko H, Koyama A, Eguchi H, Tsujino A, Ikeuchi T, Kakita A, Okamoto K, Nishizawa M, Takahashi H, Onodera O (2008) TDP-43 mutation in familial amyotrophic lateral sclerosis. Ann Neurol 63:538–542

    Article  CAS  PubMed  Google Scholar 

  • Yoshiyama Y, Lee VM, Trojanowski JQ (2013) Therapeutic strategies for tau mediated neurodegeneration. J Neurol Neurosurg Psychiatry 84:784–795

    Article  PubMed Central  PubMed  Google Scholar 

  • Zhang Z, Lotti F, Dittmar K, Younis I, Wan L, Kasim M, Dreyfuss G (2008) SMN deficiency causes tissue-specific perturbations in the repertoire of snRNAs and widespread defects in splicing. Cell 133:585–600

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zu T, Gibbens B, Doty NS, Gomes-Pereira M, Huguet A, Stone MD, Margolis J, Peterson M, Markowski TW, Ingram MA, Nan Z, Forster C, Low WC, Schoser B, Somia NV, Clark HB, Schmechel S, Bitterman PB, Gourdon G, Swanson MS, Moseley M, Ranum LP (2011) Non-ATG-initiated translation directed by microsatellite expansions. Proc Natl Acad Sci U S A 108:260–265

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Bioresources, Brain Research Institute, Niigata University, Niigata, Japan

    Tomohiko Ishihara & Osamu Onodera

  2. Clinical Neuroscience Branch, Brain Research Institute, Niigata University, Niigata, Japan

    Masatoyo Nishizawa

Authors
  1. Tomohiko Ishihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masatoyo Nishizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Osamu Onodera
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Osamu Onodera .

Editor information

Editors and Affiliations

  1. National Center of Neurology and Psychiatry, Kodaira, Japan

    Keiji Wada

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Japan

About this chapter

Cite this chapter

Ishihara, T., Nishizawa, M., Onodera, O. (2015). Conformational Disease and RNA Disease Theory in the Context of Neurodegenerative Diseases. In: Wada, K. (eds) Neurodegenerative Disorders as Systemic Diseases. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54541-5_1

Download citation

Publish with us

Policies and ethics

Search

Navigation