nach oben

Neurotoxicity Research

Erschienen in:

01.10.2009

Versatile Somatic Gene Transfer for Modeling Neurodegenerative Diseases

verfasst von: Ronald L. Klein, David B. Wang, Michael A. King

Erschienen in: Neurotoxicity Research | Ausgabe 3/2009

Einloggen, um Zugang zu erhalten

Abstract

A growing variety of technical approaches allow control over the expression of selected genes in living organisms. The ability to deliver functional exogenous genes involved in neurodegenerative diseases has opened pathological processes to experimental analysis and targeted therapeutic development in rodent and primate preclinical models. Biological adaptability, economic animal use, and reduced model development costs complement improved control over spatial and temporal gene expression compared with conventional transgenic models. A review of viral vector studies, typically adeno-associated virus or lentivirus, for expression of three proteins that are central to major neurodegenerative diseases, will illustrate how this approach has powered new advances and opportunities in CNS disease research.

Ajmani PS, Wang W, Tang F, King MA, Meyer EM, Hughes JA (2001) Transgene delivery with a cationic lipid in the presence of amyloid beta (betaAP) peptide. Neurochem Res 26(3):195–202PubMedCrossRef

Askanas V, McFerrin J, Baqué S, Alvarez RB, Sarkozi E, Engel WK (1996) Transfer of beta-amyloid precursor protein gene using adenovirus vector causes mitochondrial abnormalities in cultured normal human muscle. Proc Natl Acad Sci USA 93(3):1314–1319PubMedCrossRef

Auluck PK, Chan HY, Trojanowski JQ, Lee VM, Bonini NM (2002) Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson’s disease. Science 295(5556):865–868PubMedCrossRef

Ballatore C, Lee VM, Trojanowski JQ (2007) Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci 8(9):663–672PubMedCrossRef

Bayer TA, Fossgreen A, Czech C, Beyreuther K, Wiestler OD (1996) Plaque formation in brain transplants exposed to human beta-amyloid precursor protein 695. Acta Neuropathol 92(2):130–137PubMedCrossRef

Bayer TA, Breyhan H, Duan K, Rettig J, Wirths O (2008) Intraneuronal beta-amyloid is a major risk factor—novel evidence from the APP/PS1KI mouse model. Neurodegener Dis 5(3–4):140–142PubMedCrossRef

Bilang-Bleuel A, Revah F, Colin P, Locquet I, Robert JJ, Mallet J, Horellou P (1997) Intrastriatal injection of an adenoviral vector expressing glial-cell-line-derived neurotrophic factor prevents dopaminergic neuron degeneration and behavioral impairment in a rat model of Parkinson disease. Proc Natl Acad Sci USA 94(16):8818–8823PubMedCrossRef

Blömer U, Naldini L, Kafri T, Trono D, Verma IM, Gage FH (1997) Highly efficient and sustained gene transfer in adult neurons with a lentivirus vector. J Virol 71(9):6641–6649PubMed

Borchelt DR, Davis J, Fischer M, Lee MK, Slunt HH, Ratovitsky T, Regard J, Copeland NG, Jenkins NA, Sisodia SS, Price DL (1996) A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet Anal 13(6):159–163PubMed

Brunden KR, Trojanowski JQ, Lee VM (2008) Evidence that non-fibrillar tau causes pathology linked to neurodegeneration and behavioral impairments. J Alzheimers Dis 14(4):393–399PubMed

Burger C, Gorbatyuk OS, Velardo MJ, Peden CS, Williams P, Zolotukhin S, Reier PJ, Mandel RJ, Muzyczka N (2004) Recombinant AAV viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous system. Mol Ther 10(2):302–317PubMedCrossRef

Carty NC, Nash K, Lee D, Mercer M, Gottschall PE, Meyers C, Muzyczka N, Gordon MN, Morgan D (2008) Adeno-associated viral (AAV) serotype 5 vector mediated gene delivery of endothelin-converting enzyme reduces Abeta deposits in APP + PS1 transgenic mice. Mol Ther 16(9):1580–1586PubMedCrossRef

Castel-Barthe MN, Jazat-Poindessous F, Barneoud P, Vigne E, Revah F, Mallet J, Lamour Y (1996) Direct intracerebral nerve growth factor gene transfer using a recombinant adenovirus, effect on basal forebrain cholinergic neurons during aging. Neurobiol Dis 3(1):76–86PubMedCrossRef

Castellani RJ, Nunomura A, Lee HG, Perry G, Smith MA (2008) Phosphorylated tau: toxic, protective, or none of the above. J Alzheimers Dis 14(4):377–383PubMed

Chesselet MF (2008) In vivo alpha-synuclein overexpression in rodents: a useful model of Parkinson’s disease? Exp Neurol 209(1):22–27PubMedCrossRef

Chiang PK, Lam MA, Luo Y (2008) The many faces of amyloid beta in Alzheimer’s disease. Curr Mol Med 8(6):580–584PubMedCrossRef

Choi-Lundberg DL, Lin Q, Chang YN, Chiang YL, Hay CM, Mohajeri H, Davidson BL, Bohn MC (1997) Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science 275(5301):838–841PubMedCrossRef

Chung CY, Koprich JB, Siddiqi H, Isacson O (2009) Dynamic changes in presynaptic and axonal transport proteins combined with striatal neuroinflammation precede dopaminergic neuronal loss in a rat model of AAV alpha-synucleinopathy. J Neurosci 29(11):3365–3373PubMedCrossRef

Citron M, Oltersdorf T, Haass C, McConlogue L, Hung AY, Seubert P, Vigo-Pelfrey C, Lieberburg I, Selkoe DJ (1992) Mutation of the beta-amyloid precursor protein in familial Alzheimer’s disease increases beta-protein production. Nature 360(6405):672–674PubMedCrossRef

Congdon EE, Duff KE (2008) Is tau aggregation toxic or protective? J Alzheimers Dis 14(4):453–457PubMed

Davidson BL, Stein CS, Heth JA, Martins I, Kotin RM, Derksen TA, Zabner J, Ghodsi A, Chiorini JA (2000) Recombinant adeno-associated virus type 2, 4, and 5 vectors: transduction of variant cell types and regions in the mammalian central nervous system. Proc Natl Acad Sci USA 97(7):3428–3432PubMedCrossRef

De Strooper B, Simons M, Multhaup G, Van Leuven F, Beyreuther K, Dotti CG (1995) Production of intracellular amyloid-containing fragments in hippocampal neurons expressing human amyloid precursor protein and protection against amyloidogenesis by subtle amino acid substitutions in the rodent sequence. EMBO J 14(20):4932–4938PubMed

De Vos KJ, Grierson AJ, Ackerley S, Miller CC (2008) Role of axonal transport in neurodegenerative diseases. Annu Rev Neurosci 31:151–173PubMedCrossRef

Di Maria E, Tabaton M, Vigo T, Abbruzzese G, Bellone E, Donati C, Frasson E, Marchese R, Montagna P, Munoz DG, Pramstaller PP, Zanusso G, Ajmar F, Mandich P (2000) Corticobasal degeneration shares a common genetic background with progressive supranuclear palsy. Ann Neurol 47:374–377PubMedCrossRef

Dickson DW (1999) Tau and synuclein and their role in neuropathology. Brain Pathol 9:657–661PubMed

Dodart JC, Marr RA, Koistinaho M, Gregersen BM, Malkani S, Verma IM, Paul SM (2005) Gene delivery of human apolipoprotein E alters brain Abeta burden in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 102(4):1211–1216PubMedCrossRef

Dong Z, Ferger B, Paterna JC, Vogel D, Furler S, Osinde M, Feldon J, Büeler H (2003) Dopamine-dependent neurodegeneration in rats induced by viral vector-mediated overexpression of the parkin target protein, CDCrel-1. Proc Natl Acad Sci USA 100(21):12438–12443PubMedCrossRef

Dong Z, Wolfer DP, Lipp HP, Büeler H (2005) Hsp70 gene transfer by adeno-associated virus inhibits MPTP-induced nigrostriatal degeneration in the mouse model of Parkinson disease. Mol Ther 11(1):80–88PubMedCrossRef

Duff K, McGuigan A, Huxley C, Schulz F, Hardy J (1994) Insertion of a pathogenic mutation into a yeast artificial chromosome containing the human amyloid precursor protein gene. Gene Ther 1(1):70–75PubMed

During MJ, Naegele JR, O’Malley KL, Geller AI (1994) Long-term behavioral recovery in parkinsonian rats by an HSV vector expressing tyrosine hydroxylase. Science 266(5189):1399–1403PubMedCrossRef

Duyckaerts C, Potier MC, Delatour B (2008) Alzheimer disease models and human neuropathology: similarities and differences. Acta Neuropathol 115(1):5–38PubMedCrossRef

Eckert A, Steiner B, Marques C, Leutz S, Romig H, Haass C, Müller WE (2001) Elevated vulnerability to oxidative stress-induced cell death and activation of caspase-3 by the Swedish amyloid precursor protein mutation. J Neurosci Res 64(2):183–192PubMedCrossRef

Eslamboli A, Romero-Ramos M, Burger C, Bjorklund T, Muzyczka N, Mandel RJ, Baker H, Ridley RM, Kirik D (2007) Long-term consequences of human alpha-synuclein overexpression in the primate ventral midbrain. Brain 130(3):799–815PubMedCrossRef

Feany MB, Bender WW (2000) A Drosophila model of Parkinson’s disease. Nature 404(6776):394–398PubMedCrossRef

Federoff HJ, Geschwind MD, Geller AI, Kessler JA (1992) Expression of nerve growth factor in vivo from a defective herpes simplex virus 1 vector prevents effects of axotomy on sympathetic ganglia. Proc Natl Acad Sci USA 89(5):1636–1640PubMedCrossRef

Frazer ME, Hughes JE, Mastrangelo MA, Tibbens JL, Federoff HJ, Bowers WJ (2008) Reduced pathology and improved behavioral performance in Alzheimer’s disease mice vaccinated with HSV amplicons expressing amyloid-beta and interleukin-4. Mol Ther 16(5):845–853PubMedCrossRef

Fukuchi K, Kamino K, Deeb SS, Furlong CE, Sundstrom JA, Smith AC, Martin GM (1992) Expression of a carboxy-terminal region of the beta-amyloid precursor protein in a heterogeneous culture of neuroblastoma cells: evidence for altered processing and selective neurotoxicity. Brain Res Mol Brain Res 16(1–2):37–46PubMedCrossRef

Fukuchi KI, Kunkel DD, Schwartzkroin PA, Kamino K, Ogburn CE, Furlong CE, Martin GM (1994) Overexpression of a C-terminal portion of the beta-amyloid precursor protein in mouse brains by transplantation of transformed neuronal cells. Exp Neurol 127(2):253–264PubMedCrossRef

Fukuchi K, Tahara K, Kim HD, Maxwell JA, Lewis TL, Accavitti-Loper MA, Kim H, Ponnazhagan S, Lalonde R (2006) Anti-Abeta single-chain antibody delivery via adeno-associated virus for treatment of Alzheimer’s disease. Neurobiol Dis 23(3):502–511PubMedCrossRef

Furler S, Paterna JC, Weibel M, Büeler H (2001) Recombinant AAV vectors containing the foot and mouth disease virus 2A sequence confer efficient bicistronic gene expression in cultured cells and rat substantia nigra neurons. Gene Ther 8(11):864–873PubMedCrossRef

Geller AI, Breakefield XO (1988) A defective HSV-1 vector expresses Escherichia coli beta-galactosidase in cultured peripheral neurons. Science 241(4873):1667–1669PubMedCrossRef

Gibrat C, Saint-Pierre M, Bousquet M, Lévesque D, Rouillard C, Cicchetti F (2009) Differences between subacute and chronic MPTP mice models: investigation of dopaminergic neuronal degeneration and alpha-synuclein inclusions. J Neurochem 109(5):1469–1482PubMedCrossRef

Gong Y, Meyer EM, Meyers CA, Klein RL, King MA, Hughes JA (2006) Memory-related deficits following selective hippocampal expression of Swedish mutation amyloid precursor protein in the rat. Exp Neurol 200(2):371–377PubMedCrossRef

Gorbatyuk OS, Li S, Sullivan LF, Chen W, Kondrikova G, Manfredsson FP, Mandel RJ, Muzyczka N (2008) The phosphorylation state of Ser-129 in human alpha-synuclein determines neurodegeneration in a rat model of Parkinson disease. Proc Natl Acad Sci USA 105(2):763–768PubMedCrossRef

Grimm D, Kern A, Rittner K, Kleinschmidt JA (1998) Novel tools for production and purification of recombinant adenoassociated virus vectors. Hum Gene Ther 9(18):2745–2760PubMedCrossRef

Hacein-Bey-Abina S, Garrigue A, Wang GP, Soulier J, Lim A, Morillon E et al (2008) Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest 118:3132–3142PubMedCrossRef

Hall GF, Yao J (2005) Modeling tauopathy: a range of complementary approaches. Biochim Biophys Acta (BBA) (Mol Basis Disease) 1739(2–3):224–239CrossRef

Hamamichi S, Rivas RN, Knight AL, Cao S, Caldwell KA, Caldwell GA (2008) Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson’s disease model. Proc Natl Acad Sci USA 105(2):728–733PubMedCrossRef

Hayashita-Kinoh H, Yamada M, Yokota T, Mizuno Y, Mochizuki H (2006) Down-regulation of alpha-synuclein expression can rescue dopaminergic cells from cell death in the substantia nigra of Parkinson’s disease rat model. Biochem Biophys Res Commun 341(4):1088–1095PubMedCrossRef

Heng MY, Detloff PJ, Albin RL (2008) Rodent genetic models of Huntington disease. Neurobiol Dis 32:1–9PubMedCrossRef

Hong CS, Goins WF, Goss JR, Burton EA, Glorioso JC (2006) Herpes simplex virus RNAi and neprilysin gene transfer vectors reduce accumulation of Alzheimer’s disease-related amyloid-beta peptide in vivo. Gene Ther 13(14):1068–1079PubMedCrossRef

Horellou P, Vigne E, Castel MN, Barnéoud P, Colin P, Perricaudet M, Delaère P, Mallet J (1994) Direct intracerebral gene transfer of an adenoviral vector expressing tyrosine hydroxylase in a rat model of Parkinson’s disease. NeuroReport 6(1):49–53PubMedCrossRef

Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A et al (1998) Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393:702–705PubMedCrossRef

Iqbal K, Alonso AC, Chen S, Chohan MO, El-Akkad E, Gong CX, Khatoon S, Li B, Liu F, Rahman A, Tanimukai H, Grundke-Iqbal I (2005) Tau pathology in Alzheimer disease and other tauopathies. Biochim Biophys Acta 1739(2–3):198–210PubMed

Iqbal K, Liu F, Gong CX, Alonso AC, Grundke-Iqbal I (2009) Mechanisms of tau-induced neurodegeneration. Acta Neuropathol 118(1):53–69PubMedCrossRef

Iwata N, Mizukami H, Shirotani K, Takaki Y, Muramatsu S, Lu B, Gerard NP, Gerard C, Ozawa K, Saido TC (2004) Presynaptic localization of neprilysin contributes to efficient clearance of amyloid-beta peptide in mouse brain. J Neurosci 24(4):991–998PubMedCrossRef

Jellinger KA (2003) Neuropathological spectrum of synucleinopathies. Mov Disord 18(Suppl 6):S2–S12PubMedCrossRef

Jung AE, Fitzsimons HL, Bland RJ, During MK, Young D (2008) HSP70 and constitutively active HSF1 mediate protection against CDCrel-1-mediated toxicity. Mol Ther 16(6):1048–1055PubMedCrossRef

Kahle PJ (2008) alpha-Synucleinopathy models and human neuropathology: similarities and differences. Acta Neuropathol 115(1):87–95PubMedCrossRef

Kaplitt MG, Leone P, Samulski RJ, Xiao X, Pfaff DW, O’Malley KL, During MJ (1994) Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat Genet 8(2):148–154PubMedCrossRef

Kindy MS, King AR, Yu J, Gerardot C, Whitley J, de Beer FC (1998) Adenoviral expression of murine serum amyloid A proteins to study amyloid fibrillogenesis. Biochem J 332(Pt 3):721–728PubMed

Kirik D, Björklund A (2003) Modeling CNS neurodegeneration by overexpression of disease-causing proteins using viral vectors. Trends Neurosci 26(7):386–392PubMedCrossRef

Kirik D, Rosenblad C, Burger C, Lundberg C, Johansen TE, Muzyczka N, Mandel RJ, Björklund A (2002) Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system. J Neurosci 22(7):2780–2791PubMed

Kirik D, Annett LE, Burger C, Muzyczka N, Mandel RJ, Björklund A (2003) Nigrostriatal alpha-synucleinopathy induced by viral vector-mediated overexpression of human alpha-synuclein: a new primate model of Parkinson’s disease. Proc Natl Acad Sci USA 100(5):2884–2889PubMedCrossRef

Kitao Y, Imai Y, Ozawa K, Kataoka A, Ikeda T, Soda M, Nakimawa K, Kiyama H, Stern DM, Hori O, Wakamatsu K, Ito S, Itohara S, Takahashi R, Ogawa S (2007) Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of parkin inactivation. Hum Mol Genet 16(1):50–60PubMedCrossRef

Klein RL, Meyer EM, Peel AL, Zolotukhin S, Meyers C, Muzyczka N, King MA (1998) Neuron-specific transduction in the rat septohippocampal or nigrostriatal pathway by recombinant adeno-associated virus vectors. Exp Neurol 150:183–194PubMedCrossRef

Klein RL, Hamby ME, Hirko AC, Gong Y, Wang S, Hughes J, King MA, Meyer EM (2002a) Dose and promoter effects of adeno-associated viral vector for green fluorescent protein expression in the rat brain. Exp Neurol 176:66–74PubMedCrossRef

Klein RL, King MA, Hamby ME, Meyer EM (2002b) Dopaminergic cell loss induced by human A30P alpha-synuclein gene transfer to the rat substantia nigra. Hum Gene Ther 13:605–612PubMedCrossRef

Klein RL, Lin WL, Dickson DW, Lewis J, Hutton M, Duff K, Meyer EM, King MA (2004) Rapid neurofibrillary tangle formation after localized gene transfer of mutated tau. Am J Pathol 164:347–353PubMed

Klein RL, Dayton RD, Lin WL, Dickson DW (2005) Tau gene transfer, but not alpha-synuclein, induces both progressive dopamine neuron degeneration and rotational behavior in the rat. Neurobiol Dis 20:64–73PubMedCrossRef

Klein RL, Dayton RD, Henderson KM, Petrucelli L (2006a) Parkin is protective for substantia nigra dopamine neurons in a tau gene transfer neurodegeneration model. Neurosci Lett 401:130–135PubMedCrossRef

Klein RL, Dayton RD, Leidenheimer NJ, Jansen K, Golde TE, Zweig RW (2006b) Efficient neuronal gene transfer with AAV8 leads to neurotoxic levels of tau or green fluorescent proteins. Mol Ther 13:517–527PubMedCrossRef

Klein RL, Dayton RD, Tatom JB, Diaczynsky CG, Salvatore MF (2008a) Tau expression levels from various adeno-associated virus vector serotypes produce graded neurodegenerative disease states. Eur J NeuroSci 27:1615–1625PubMedCrossRef

Klein RL, Dayton RD, Tatom JB, Henderson KM, Henning PP (2008b) AAV 8, 9, Rh10, Rh43 vector gene transfer in the rat brain: effects of serotype, promoter and purification method. Mol Ther 16:89–96PubMedCrossRef

Klein RL, Dayton RD, Diaczynsky CG, Wang DB (2009) Pronounced microgliosis and neurodegeneration in aged rats after tau gene transfer. Neurobiol Aging [Epub ahead of print]

Krenz A, Falkenburger BH, Gerhardt E, Drinkut A, Schulz JB (2009) Aggregate formation and toxicity by wild-type and R621C synphilin-1 in the nigrostriatal system of mice using adenoviral vectors. J Neurochem 108(1):139–146PubMedCrossRef

Kulnane LS, Lamb BT (2001) Neuropathological characterization of mutant amyloid precursor protein yeast artificial chromosome transgenic mice. Neurobiol Dis 8(6):982–992PubMedCrossRef

Lakso M, Vartiainen S, Moilanen AM, Sirviö J, Thomas JH, Nass R, Blakely RD, Wong G (2003) Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human alpha-synuclein. J Neurochem 86(1):165–172PubMedCrossRef

Lamb BT, Call LM, Slunt HH, Bardel KA, Lawler AM, Eckman CB, Younkin SG, Holtz G, Wagner SL, Price DL, Sisodia SS, Gearhart JD (1997) Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice. Hum Mol Genet 6(9):1535–1541

LaPointe NE, Morfini G, Pigino G, Gaisina IN, Kozikowski AP, Binder LI, Brady ST (2009) The amino terminus of tau inhibits kinesin-dependent axonal transport: implications for filament toxicity. J Neurosci Res 87(2):440–451PubMedCrossRef

Lawlor PA, Bland RJ, Das P, Price RW, Holloway V, Smithson L, Dicker BL, During MJ, Young D, Golde TE (2007) Novel rat Alzheimer’s disease models based on AAV-mediated gene transfer to selectively increase hippocampal Abeta levels. Mol Neurodegener 2:11PubMedCrossRef

Le Gal La Salle G, Robert JJ, Berrard S, Ridoux V, Stratford-Perricaudet LD, Perricaudet M, Mallet J (1993) An adenovirus vector for gene transfer into neurons and glia in the brain. Science 259(5097):988–990PubMedCrossRef

Lee VM, Kenyon TK, Trojanowski JQ (2005) Transgenic animal models of tauopathies. Biochim Biophys Acta 1739:251–259PubMed

Levites Y, Jansen K, Smithson LA, Dakin R, Holloway VM, Das P, Golde TE (2006) Intracranial adeno-associated virus-mediated delivery of anti-pan amyloid beta, amyloid beta40, and amyloid beta42 single-chain variable fragments attenuates plaque pathology in amyloid precursor protein mice. J Neurosci 26(46):11923–11928. Erratum in J Neurosci (2006) 26(49), preceding 12847

Lewis J, McGowan E, Rockwood J, Melrose H, Nacharaju P, Van Slegtenhorst M, Gwinn-Hardy K, Paul Murphy M, Baker M, Yu X, Duff K, Hardy J, Corral A, Lin WL, Yen SH, Dickson DW, Davies P, Hutton M (2000) Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat Genet 25(4):402–405PubMedCrossRef

Li Z, Dullmann J, Schiedlmeier B, Schmidt M, von Kalle C, Meyer J et al (2002) Murine leukemia induced by retroviral gene marking. Science 296:497PubMedCrossRef

Liang J, Clark-Dixon C, Wang S, Flower TR, Williams-Hart T, Zweig R, Robinson LC, Tatchell K, Witt SN (2008) Novel suppressors of alpha-synuclein toxicity identified using yeast. Hum Mol Genet 17(23):3784–3795PubMedCrossRef

Lo Bianco C, Ridet JL, Schneider BL, Deglon N, Aebischer P (2002) alpha-Synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson’s disease. Proc Natl Acad Sci USA 99(16):10813–10818PubMedCrossRef

Lo Bianco C, Déglon N, Pralong W, Aebischer P (2004a) Lentiviral nigral delivery of GDNF does not prevent neurodegeneration in a genetic rat model of Parkinson’s disease. Neurobiol Dis 17(2):283–289PubMedCrossRef

Lo Bianco C, Schneider BL, Bauer M, Sajadi A, Brice A, Iwatsubo T, Aebischer P (2004b) Lentiviral vector delivery of parkin prevents dopaminergic degeneration in an alpha-synuclein rat model of Parkinson’s disease. Proc Natl Acad Sci USA 101(50):17510–17515PubMedCrossRef

Lo Bianco C, Shorter J, Régulier E, Lashuel H, Iwatsubo T, Lindquist S, Aebischer P (2008) Hsp104 antagonizes alpha-synuclein aggregation and reduces dopaminergic degeneration in a rat model of Parkinson disease. J Clin Invest 118(9):3087–3097PubMedCrossRef

Lo WD, Qu G, Sferra TJ, Clark R, Chen R, Johnson PR (1999) Adeno-associated virus-mediated gene transfer to the brain: duration and modulation of expression. Hum Gene Ther 10(2):201–213PubMedCrossRef

Lundberg C, Björklund T, Carlsson T, Jakobsson J, Hantraye P, Déglon N, Kirik D (2008) Applications of lentiviral vectors for biology and gene therapy of neurological disorders. Curr Gene Ther 8(6):461–473PubMedCrossRef

Luo JJ, Wallace W, Riccioni T, Ingram DK, Roth GS, Kusiak JW (1999) Death of PC12 cells and hippocampal neurons induced by adenoviral-mediated FAD human amyloid precursor protein gene expression. J Neurosci Res 55(5):629–642PubMedCrossRef

Lynn BD, Marotta CA, Nagy JI (1995) Propagation of intercellular calcium waves in PC12 cells overexpressing a carboxy-terminal fragment of amyloid precursor protein. Neurosci Lett 199(1):21–24PubMedCrossRef

Magrané J, Rosen KM, Smith RC, Walsh K, Gouras GK, Querfurth HW (2005) Intraneuronal beta-amyloid expression downregulates the Akt survival pathway and blunts the stress response. J Neurosci 25(47):10960–10969PubMedCrossRef

Mandel RJ, Spratt SK, Snyder RO, Leff SE (1997) Midbrain injection of recombinant adeno-associated virus encoding rat glial cell line-derived neurotrophic factor protects nigral neurons in a progressive 6-hydroxydopamine-induced degeneration model of Parkinson’s disease in rats. Proc Natl Acad Sci USA 94(25):14083–14088PubMedCrossRef

Manfredsson FP, Burger C, Sullivan LF, Muzyczka N, Lewin AS, Mandel RJ (2007) rAAV-mediated nigral human parkin over-expression partially ameliorates motor deficits via enhanced dopamine neurotransmission in a rat model of Parkinson’s disease. Exp Neurol 207(2):289–301PubMedCrossRef

Marotta CA, Chou WG, Majocha RE, Watkins R, LaBonne C, Zain SB (1989) Overexpression of amyloid precursor protein A4 (beta-amyloid) immunoreactivity in genetically transformed cells: implications for a cellular model of Alzheimer amyloidosis. Proc Natl Acad Sci USA 86(1):337–341PubMedCrossRef

Martin LJ (2007) Transgenic mice with human mutant genes causing Parkinson’s disease and amyotrophic lateral sclerosis provide common insight into mechanisms of motor neuron selective vulnerability to degeneration. Rev Neurosci 18(2):115–136PubMed

Masliah E, Rockenstein E, Veinbergs I, Mallory M, Hashimoto M, Takeda A, Sagara Y, Sisk A, Mucke L (2000) Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 287(5456):1265–1269PubMedCrossRef

Masumura M, Hata R, Nishimura I, Uetsuki T, Sawada T, Yoshikawa K (2000) Caspase-3 activation and inflammatory responses in rat hippocampus inoculated with a recombinant adenovirus expressing the Alzheimer amyloid precursor protein. Brain Res Mol Brain Res 80(2):219–227PubMedCrossRef

McCown TJ, Xiao X, Li J, Breese GR, Samulski RJ (1996) Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector. Brain Res 713(1–2):99–107PubMedCrossRef

McFarland NR, Fan Z, Xu K, Schwarzschild MA, Feany MB, Hyman BT, McLean PJ (2009) Alpha-synuclein S129 phosphorylation mutants do not alter nigrostriatal toxicity in a rat model of Parkinson disease. J Neuropathol Exp Neurol 68(5):515–524PubMedCrossRef

Mirra SS, Murrell JR, Gearing M, Spillantini MG, Goedert M, Crowther RA, Levey AI, Jones R, Green J, Shoffner JM, Wainer BH, Schmidt ML, Trojanowski JQ, Ghetti B (1999) Tau pathology in a family with dementia and a P301L mutation in tau. J Neuropathol Exp Neurol 58:335–345PubMedCrossRef

Modlich U, Baum C (2009) Preventing and exploiting the oncogenic potential of integrating gene vectors. J Clin Invest 19(4):755–758CrossRef

Moore DJ, Dawson TM (2008) Value of genetic models in understanding the cause and mechanisms of Parkinson’s disease. Curr Neurol Neurosci Rep 8(4):288–296PubMedCrossRef

Mouri A, Noda Y, Hara H, Mizoguchi H, Tabira T, Nabeshima T (2007) Oral vaccination with a viral vector containing Abeta cDNA attenuates age-related Abeta accumulation and memory deficits without causing inflammation in a mouse Alzheimer model. FASEB J 21(9):2135–2148PubMedCrossRef

Naldini L, Blömer U, Gage FH, Trono D, Verma IM (1996) Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc Natl Acad Sci USA 93(21):11382–11388PubMedCrossRef

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(5796):130–133PubMedCrossRef

Neve RL, Kammesheidt A, Hohmann CF (1992) Brain transplants of cells expressing the carboxyl-terminal fragment of the Alzheimer amyloid protein precursor cause specific neuropathology in vivo. Proc Natl Acad Sci USA 89(8):3448–3452PubMedCrossRef

Ohyagi Y (2008) Intracellular amyloid beta-protein as a therapeutic target for treating Alzheimer’s disease. Curr Alzheimer Res 5(6):555–561PubMedCrossRef

Osinde M, Clavaguera F, May-Nass R, Tolnay M, Dev KK (2008) Lentivirus Tau (P301S) expression in adult amyloid precursor protein (APP)-transgenic mice leads to tangle formation. Neuropathol Appl Neurobiol 34(5):523–531PubMedCrossRef

Outeiro TF, Lindquist S (2003) Yeast cells provide insight into alpha-synuclein biology and pathobiology. Science 302(5651):1772–1775PubMedCrossRef

Pearson BE, Choi TK (1993) Expression of the human beta-amyloid precursor protein gene from a yeast artificial chromosome in transgenic mice. Proc Natl Acad Sci USA 90(22):10578–10582PubMedCrossRef

Peel AL, Zolotukhin S, Schrimsher GW, Muzyczka N, Reier PJ (1997) Efficient transduction of green fluorescent protein in spinal cord neurons using adeno-associated virus vectors containing cell type-specific promoters. Gene Ther 4(1):16–24PubMedCrossRef

Poewe W (2009) Treatments for Parkinson disease—past achievements and current clinical needs. Neurology 72(7 Suppl):S65–S73PubMedCrossRef

Polymeropoulos MH, Higgins JJ, Golbe LI, Johnson WG, Ide SE, Di Iorio G, Sanges G, Stenroos ES, Pho LT, Schaffer AA, Lazzarini AM, Nussbaum RL, Duvoisin RC (1996) Mapping of a gene for Parkinson’s disease to chromosome 4q21–q23. Science 274(5290):1197–1199PubMedCrossRef

Poorkaj P, Bird TD, Wijsman E, Nemens E, Garruto RM, Anderson L, Andreadis A, Wiederholt WC, Raskind M, Schellenberg GD (1998) Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol 43(6):815–825PubMedCrossRef

Poorkaj P, Muma NA, Zhukareva V, Cochran EJ, Shannon KM, Hurtig H, Koller WC, Bird TD, Trojanowski JQ, Lee VM, Schellenberg GD (2002) An R5L tau mutation in a subject with a progressive supranuclear palsy phenotype. Ann Neurol 52:511–516PubMedCrossRef

Quintanilla RA, Matthews-Roberson TA, Dolan PJ, Johnson GV (2009) Caspase-cleaved tau expression results in mitochondrial dysfunction in cortical neurons. Implications for the pathogenesis of Alzheimer disease. J Biol Chem, Apr 23 [Epub ahead of print]

Rafii MS, Aisen PS (2009) Recent developments in Alzheimer’s disease therapeutics. BMC Med 7:7PubMedCrossRef

Rockenstein E, Crews L, Masliah E (2007) Transgenic animal models of neurodegenerative diseases and their application to treatment development. Adv Drug Deliv Rev 59(11):1093–1102PubMedCrossRef

Sandhu FA, Salim M, Zain SB (1991) Expression of the human beta-amyloid protein of Alzheimer’s disease specifically in the brains of transgenic mice. J Biol Chem 266(32):21331–21334PubMed

Schneider JA, Bienias JL, Gilley DW, Kvarnberg DE, Mufson EJ, Bennett DA (2002) Improved detection of substantia nigra pathology in Alzheimer’s disease. J Histochem Cytochem 50:99–106PubMed

Schupf N, Patel B, Pang D, Zigman WB, Silverman W, Mehta PD, Mayeux R (2007) Elevated plasma beta-amyloid peptide Abeta(42) levels, incident dementia, and mortality in Down syndrome. Arch Neurol 64:1007–1013PubMedCrossRef

Senut MC, Suhr ST, Kaspar B, Gage FH (2000) Intraneuronal aggregate formation and cell death after viral expression of expanded polyglutamine tracts in the adult rat brain. J Neurosci 20(1):219–229PubMed

Shaughnessy L, Thomas MB, Wakefield J, Chamblin B, Nair A, Koentgen F, Ramabhadran R (2005) Lentiviral vector-based models of amyloid pathology: from cells to animals. Curr Alzheimer Res 2(2):239–247PubMedCrossRef

Shimura H, Schlossmacher MG, Hattori N, Frosch MP, Trockenbacher A, Schneider R, Mizuno Y, Kosik KS, Selkoe DJ (2001) Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson’s disease. Science 293(5528):263–269PubMedCrossRef

Singer O, Marr RA, Rockenstein E, Crews L, Coufal NG, Gage FH, Verma IM, Masliah E (2005) Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model. Nat Neurosci 8(10):1343–1349PubMedCrossRef

Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R et al (2003) alpha-Synuclein locus triplication causes Parkinson’s disease. Science 302:841PubMedCrossRef

Spencer B, Marr RA, Rockenstein E, Crews L, Adame A, Potkar R, Patrick C, Gage FH, Verma IM, Masliah E (2008) Long-term neprilysin gene transfer is associated with reduced levels of intracellular Abeta and behavioral improvement in APP transgenic mice. BMC Neurosci 9:109PubMedCrossRef

Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388(6645):839–840PubMedCrossRef

Spillantini MG, Crowther RA, Kamphorst W, Heutink P, van Swieten JC (1998a) Tau pathology in two Dutch families with mutations in the microtubule-binding region of tau. Am J Pathol 153(5):1359–1363PubMed

Spillantini MG, Crowther RA, Jakes R, Masegawa M, Goedert M (1998b) alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with lewy bodies. Proc Natl Acad Sci USA 95(11):6469–6473PubMedCrossRef

Spires-Jones TL, Stoothoff WH, de Calignon A, Jones PB, Hyman BT (2009) Tau pathophysiology in neurodegeneration: a tangled issue. Trends Neurosci 32(3):150–159PubMedCrossRef

St Martin JL, Klucken J, Outeiro TF, Nguyen P, Keller-McGandy C, Cantuti-Castelvetri I, Grammatopoulos TN, Standaert DG, Hyman BT, McLean PJ (2007) Dopaminergic neuron loss and up-regulation of chaperone protein mRNA induced by targeted over-expression of alpha-synuclein in mouse substantia nigra. J Neurochem 100(6):1449–1457PubMed

Szerlip NJ, Walbridge S, Yang L, Morrison PF, Degen JW, Jarrell ST, Kouri J, Kerr PB, Kotin R, Oldfield EH, Lonser RR (2007) Real-time imaging of convection-enhanced delivery of viruses and virus-sized particles. J Neurosurg 107(3):560–567PubMedCrossRef

Tatom JB, Wang DB, Dayton RD, Hutton ML, Dickson DW, Klein RL (2009) Mimicking aspects of frontotemporal lobar degeneration and Lou Gehrig’s disease in rats via TDP-43 overexpression. Mol Ther 17(4):607–613PubMedCrossRef

Terwel D, Muyllaert D, Dewachter I, Borghgraef P, Croes S, Devijver H, Van Leuven F (2008) Amyloid activates GSK-3beta to aggravate neuronal tauopathy in bigenic mice. Am J Pathol 172(3):786–798PubMedCrossRef

Thomas B, Beal MF (2007) Parkinson’s disease. Hum Mol Genet 16(Spec No 2):R183–R194PubMedCrossRef

Uetsuki T, Takemoto K, Nishimura I, Okamoto M, Niinobe M, Momoi T, Miura M, Yoshikawa K (1999) Activation of neuronal caspase-3 by intracellular accumulation of wild-type Alzheimer amyloid precursor protein. J Neurosci 19(16):6955–6964PubMed

Vasilevko V, Cribbs DH (2006) Novel approaches for immunotherapeutic intervention in Alzheimer’s disease. Neurochem Int 49(2):113–126PubMedCrossRef

Wakabayashi K, Oyanagi K, Makifuchi T, Ikuta F, Homma A, Homma Y, Horikawa Y, Tokiguchi S (1994) Corticobasal degeneration: etiopathological significance of the cytoskeletal alterations. Acta Neuropathol 87:545–553PubMedCrossRef

Wojtowicz WM, Farzan M, Joyal JL, Carter K, Babcock GJ, Israel DI, Sodroski J, Mirzabekov T (2002) Stimulation of enveloped virus infection by beta-amyloid fibrils. J Biol Chem 277(38):35019–35024 Sep 20PubMedCrossRef

Xiao X, Li J, Samulski RJ (1998) Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J Virol 72(3):2224–2232PubMed

Xu R, Janson CG, Mastakov M, Lawlor P, Young D, Mouravlev A, Fitzsimons H, Choi KL, Ma H, Dragunow M, Leone P, Chen Q, Dicker B, During MJ (2001) Quantitative comparison of expression with adeno-associated virus (AAV-2) brain-specific gene cassettes. Gene Ther 8(17):1323–1332PubMedCrossRef

Yamada M, Iwatsubo T, Mizuno Y, Mochizuki H (2004) Overexpression of alpha-synuclein in rat substantia nigra results in loss of dopaminergic neurons, phosphorylation of alpha-synuclein and activation of caspase-9: resemblance to pathogenetic changes in Parkinson’s disease. J Neurochem 91(2):451–461PubMedCrossRef

Yamada M, Mizuno Y, Mochizuki H (2005) Parkin gene therapy for alpha-synucleinopathy: a rat model of Parkinson’s disease. Hum Gene Ther 16(2):262–270PubMedCrossRef

Yasuda T, Miyachi S, Kitagawa R, Wada K, Nihira T, Ren YR, Hirai Y, Ageyama N, Terao K, Shimada T, Takada M, Mizuno Y, Mochizuki H (2007) Neuronal specificity of alpha-synuclein toxicity and effect of Parkin co-expression in primates. Neuroscience 144(2):743–753PubMedCrossRef

Zaiss AK, Muruve DA (2008) Immunity to adeno-associated virus vectors in animals and humans: a continued challenge. Gene Ther 15(11):808–816PubMedCrossRef

Zilka N, Stozicka Z, Kovac A, Pilipcinec E, Bugos O, Novak M (2009) Human misfolded truncated tau protein promotes activation of microglia and leukocyte infiltration in the transgenic rat model of tauopathy. J Neuroimmunol 209(1–2):16–25PubMedCrossRef

Zolotukhin S, Potter M, Hauswirth WW, Guy J, Muzyczka N (1996) A “humanized” green fluorescent protein cDNA adapted for high-level expression in mammalian cells. J Virol 70(7):4646–4654PubMed

Zolotukhin S, Byrne BJ, Mason E, Zolotukhin I, Potter M, Chesnut K, Summerford C, Samulski RJ, Muzyczka N (1999) Recombinant adeno-associated virus purification using novel methods improves infectious titer and yield. Gene Ther 6(6):973–985PubMedCrossRef

Zou J, Yao Z, Zhang G, Wang H, Xu J, Yew DT, Forster EL (2008) Vaccination of Alzheimer’s model mice with adenovirus vector containing quadrivalent foldable Abeta(1–15) reduces Abeta burden and behavioral impairment without Abeta-specific T cell response. J Neurol Sci 272(1–2):87–98PubMedCrossRef

Titel: Versatile Somatic Gene Transfer for Modeling Neurodegenerative Diseases
verfasst von: Ronald L. Klein
David B. Wang
Michael A. King
Publikationsdatum: 01.10.2009
Verlag: Springer-Verlag
Erschienen in: Neurotoxicity Research / Ausgabe 3/2009
Print ISSN: 1029-8428
Elektronische ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-009-9080-7

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Thrombektomie auch bei großen Infarkten von Vorteil

16.05.2024 Ischämischer Schlaganfall Nachrichten

Auch ein sehr ausgedehnter ischämischer Schlaganfall scheint an sich kein Grund zu sein, von einer mechanischen Thrombektomie abzusehen. Dafür spricht die LASTE-Studie, an der Patienten und Patientinnen mit einem ASPECTS von maximal 5 beteiligt waren.

Schwindelursache: Massagepistole lässt Otholiten tanzen

14.05.2024 Benigner Lagerungsschwindel Nachrichten

Wenn jüngere Menschen über ständig rezidivierenden Lagerungsschwindel klagen, könnte eine Massagepistole der Auslöser sein. In JAMA Otolaryngology warnt ein Team vor der Anwendung hochpotenter Geräte im Bereich des Nackens.

Schützt Olivenöl vor dem Tod durch Demenz?

10.05.2024 Morbus Alzheimer Nachrichten

Konsumieren Menschen täglich 7 Gramm Olivenöl, ist ihr Risiko, an einer Demenz zu sterben, um mehr als ein Viertel reduziert – und dies weitgehend unabhängig von ihrer sonstigen Ernährung. Dafür sprechen Auswertungen zweier großer US-Studien.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2009

Role of Tat Protein in HIV Neuropathogenesis

Additive Protective Effects of Donepezil and Nicotine Against Salsolinol-Induced Cytotoxicity in SH-SY5Y Cells

Nur(R1)turing a Notion on the Etiopathogenesis of Parkinson’s Disease

CXCR4 and CXCL12 Expression is Increased in the Nigro-Striatal System of Parkinson’s Disease

Nitric Oxide as an Initiator of Brain Lesions During the Development of Alzheimer Disease