Skip to main content

Novel Gene Therapeutic Strategies for Neurodegenerative Diseases

  • Conference paper
Opportunities and Challenges of the Therapies Targeting CNS Regeneration

Part of the book series: Ernst Schering Research Foundation Workshop ((SCHERING FOUND,volume 53))

9.5 Summary

The convergent pathobiologic model of Parkinson’s disease stipulates that disparate insults initiate a disease process that obligately share a common pathway leading to cell death. A combinatorial treatment which targets various steps in this pathway is likely to be the most successful therapeutic strategy. As advances are made in the field of neuroimaging and pharmacogenomics, early detection of sporadic PD will become a reality. Early intervention will likely sparemore dopaminergic neurons and extend the quality of life for the patient. Continued advancements in the fields of pharmacology, neurosurgery, and gene therapy will strengthen the armamentarium available for the treatment of PD patients.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ahlskog JE, Muenter MD (2001) Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord 16:448–458

    Article  PubMed  CAS  Google Scholar 

  • Akerud P, Canals JM, Snyder EY, Arenas E (2001) Neuroprotection through delivery of glial cell line-derived neurotrophic factor by neural stem cells in a mouse model of Parkinson’s disease. J Neurosci 21:8108–8118

    PubMed  CAS  Google Scholar 

  • Akerud P, Holm PC, Castelo-Branco G, Sousa K, Rodriguez FJ, Arenas E (2002) Persephin-overexpressing neural stem cells regulate the function of nigral dopaminergic neurons and prevent their degeneration in a model of Parkinson’s disease. Mol Cell Neurosci 21:205–222

    Article  PubMed  CAS  Google Scholar 

  • Antonini A, DeNotaris R (2004) PET and SPECT functional imaging in Parkinson’s disease. Sleep Med 5:201–206

    Article  PubMed  Google Scholar 

  • Aoi M, Date I, Tomita S, Ohmoto T (2000) GDNF induces recovery of the nigrostriatal dopaminergic systemin the rat brain following intracerebroventricular or intraparenchymal administration. Acta Neurochir (Wien) 142:805–810

    Article  CAS  Google Scholar 

  • Aoi M, Date I, Tomita S, Ohmoto T (2001) Single administration of GDNF into the striatum induced protection and repair of the nigrostriatal dopaminergic system in the intrastriatal 6-hydroxydopamine injection model of hemiparkinsonism. Restor Neurol Neurosci 17:31–38

    PubMed  Google Scholar 

  • Asanuma M, Ogawa N, Nishibayashi S, Kawai M, Kondo Y, Iwata E (1995) Protective effects of pergolide on dopamine levels in the 6-hydroxydopamine-lesioned mouse brain. Arch Int Pharmacodyn Ther 329:221–230

    PubMed  CAS  Google Scholar 

  • Asanuma M, Miyazaki I, Ogawa N (2003) Dopamine-or L-DOPA-induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinson’s disease. Neurotox Res 5:165–176

    Article  PubMed  Google Scholar 

  • Baba M, Nakajo S, Tu PH, Tomita T, Nakaya K, Lee VM, Trojanowski JQ, Iwatsubo T (1998) Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies. Am J Pathol 152:879–884

    PubMed  CAS  Google Scholar 

  • Beal MF (2003) Bioenergetic approaches for neuroprotection in Parkinson’s disease. Ann Neurol 53Suppl 3: S39–47; discussion S47–48

    Article  PubMed  CAS  Google Scholar 

  • Benabid AL (2003) Deep brain stimulation for Parkinson’s disease. Curr Opin Neurobiol 13:696–706

    Article  PubMed  CAS  Google Scholar 

  • Benabid AL, Benazzouz A, Hoffmann D, Limousin P, Krack P, Pollak P (1998) Long-term electrical inhibition of deep brain targets in movement disorders. Mov Disord 13Suppl 3:119–125

    PubMed  Google Scholar 

  • Benbunan BR, Korczyn AD, Giladi N (2004) Parkin mutation associated parkinsonismand cognitive decline, comparison to early onset Parkinson’s disease. J Neural Transm 111:47–57

    Article  PubMed  CAS  Google Scholar 

  • Bibbiani F, Oh JD, Petzer JP, Castagnoli N, Jr., Chen JF, Schwarzschild MA, Chase TN (2003) A2A antagonist prevents dopamine agonist-induced motor complications in animal models of Parkinson’s disease. Exp Neurol 184:285–294

    Article  PubMed  CAS  Google Scholar 

  • Bowers WJ, Maguire-Zeiss KA, Harvey BK, Federoff HJ (2001) Gene therapeutic approaches to the treatment of Parkinson’s disease. Clin Neurosci Res 1:483–495

    Article  CAS  Google Scholar 

  • Carvey PM, Pieri S, Ling ZD (1997) Attenuation of levodopa-induced toxicity in mesencephalic cultures by pramipexole. J Neural Transm 104:209–228

    Article  PubMed  CAS  Google Scholar 

  • Casteilla L, Rigoulet M, Penicaud L (2001) Mitochondrial ROS metabolism: modulation by uncoupling proteins. IUBMB Life 52:181–188

    Article  PubMed  CAS  Google Scholar 

  • Chandra S, Chen X, Rizo J, Jahn R, Sudhof TC (2003) A broken alpha-helix in folded alpha-Synuclein. J Biol Chem 278:15313–15318

    Article  PubMed  CAS  Google Scholar 

  • Chauhan NB, Siegel GJ, Lee JM (2001) Depletion of glial cell line-derived neurotrophic factor in substantia nigra neurons of Parkinson’s disease brain. J Chem Neuroanat 21:277–288

    Article  PubMed  CAS  Google Scholar 

  • Chen JF, Moratalla R, Impagnatiello F, Grandy DK, Cuellar B, Rubinstein M, Beilstein MA, Hackett E, Fink JS, Low MJ, Ongini E, Schwarzschild MA (2001) The role of the D(2) dopamine receptor (D(2)R) in A(2A) adenosine receptor (A(2A)R)-mediated behavioral and cellular responses as revealed by A(2A) and D(2) receptor knockout mice. Proc Natl Acad Sci 98:1970–5

    Article  PubMed  CAS  Google Scholar 

  • 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 275:838–841

    Article  PubMed  CAS  Google Scholar 

  • Clayton DF, George JM (1998) The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease. Trends Neurosci 21:249–254

    Article  PubMed  CAS  Google Scholar 

  • Conway KA, Rochet JC, Bieganski RM, Lansbury PT, Jr. (2001) Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Science 294:1346–1349

    Article  PubMed  CAS  Google Scholar 

  • Costa S, Iravani MM, Pearce RK, Jenner P (2001) Glial cell line-derived neurotrophic factor concentration dependently improves disability and motor activity in MPTP-treated common marmosets. Eur J Pharmacol 412:45–50

    Article  PubMed  CAS  Google Scholar 

  • Cotzias GC, Van Woert MH, Schiffer LM (1967) Aromatic amino acids and modification of parkinsonism. N Engl J Med 276:374–379

    Article  PubMed  CAS  Google Scholar 

  • Cunningham LA, Su C (2002) Astrocyte delivery of glial cell line-derived neurotrophic factor in a mouse model of Parkinson’s disease. Exp Neurol 174:230–242

    Article  PubMed  CAS  Google Scholar 

  • Date I, Shingo T, Yoshida H, Fujiwara K, Kobayashi K, Takeuchi A, Ohmoto T (2001) Grafting of encapsulated genetically modified cells secreting GDNF into the striatum of parkinsonian model rats. Cell Transplant 10:397–401

    PubMed  CAS  Google Scholar 

  • Davidson WS, Jonas A, Clayton DF, George JM (1998) Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J Biol Chem 273:9443–9449

    Article  PubMed  CAS  Google Scholar 

  • Echtay KS, Winkler E, Frischmuth K, Klingenberg M(2001) Uncoupling proteins 2 and 3 are highly active H(+) transporters and highly nucleotide sensitive when activated by coenzyme Q (ubiquinone). Proc Natl Acad Sci 98:1416–1421

    Article  PubMed  CAS  Google Scholar 

  • Eckert T, Eidelberg D (2004) The role of functional neuroimaging in the differential diagnosis of idiopathic Parkinson’s disease and multiple system atrophy. Clin Auton Res 14:84–91

    Article  PubMed  Google Scholar 

  • Emadi S, Liu R, Yuan B, Schulz P, McAllister C, Lyubchenko Y, Messer A, Sierks MR (2004) Inhibiting aggregation of alpha-synuclein with human single chain antibody fragments. Biochemistry 43:2871–2878

    Article  PubMed  CAS  Google Scholar 

  • Fahn S (2003) Description of Parkinson’s disease as a clinical syndrome. Ann N Y Acad Sci 991:1–14

    Article  PubMed  CAS  Google Scholar 

  • Fink JS, Weaver DR, Rivkees SA, Peterfreund RA, Pollack AE, Adler EM, Reppert SM (1992) Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum. Brain Res Mol Brain Res 14:186–195

    Article  PubMed  CAS  Google Scholar 

  • Forloni G, Terreni L, Bertani I, Fogliarino S, Invernizzi R, Assini A, Ribizzi G, Negro A, Calabrese E, Volonte MA, Mariani C, Franceschi M, Tabaton M, Bertoli A (2002) Protein misfolding in Alzheimer’s and Parkinson’s disease: genetics and molecular mechanisms. Neurobiol Aging 23:957

    Article  PubMed  CAS  Google Scholar 

  • Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S (2001) Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 344:710–719

    Article  PubMed  CAS  Google Scholar 

  • Gash DM, Zhang Z, Ovadia A, Cass WA, Yi A, Simmerman L, Russell D, Martin D, Lapchak PA, Collins F, Hoffer BJ, Gerhardt GA (1996) Functional recovery in parkinsonian monkeys treated with GDNF. Nature 380:252–255

    Article  PubMed  CAS  Google Scholar 

  • Gassen M, Gross A, Youdim MB (1998) Apomorphine enantiomers protect cultured pheochromocytoma (PC12) cells from oxidative stress induced by H2O2 and 6-hydroxydopamine. Mov Disord 13:661–667

    Article  PubMed  CAS  Google Scholar 

  • Gerhardt GA, Cass WA, Huettl P, Brock S, Zhang Z, Gash DM (1999) GDNF improves dopamine function in the substantia nigra but not the putamen of unilateral MPTP-lesioned rhesus monkeys. Brain Res 817:163–171

    Article  PubMed  CAS  Google Scholar 

  • Gill SS, Patel NK, Hotton GR, O’Sullivan K, McCarter R, Bunnage M, Brooks DJ, Svendsen CN, Heywood P (2003) Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med 9:589–595

    Article  PubMed  CAS  Google Scholar 

  • Glorioso JC, Mata M, Fink DJ (2003) Therapeutic gene transfer to the nervous system using viral vectors. J Neurovirol 9:165–172

    PubMed  CAS  Google Scholar 

  • Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Richardson RJ (1998) The risk of Parkinson’s disease with exposure to pesticides, farming, well water, and rural living. Neurology 50:1346–1350

    PubMed  CAS  Google Scholar 

  • Grondin R, Zhang Z, Yi A, Cass WA, Maswood N, Andersen AH, Elsberry DD, Klein MC, Gerhardt GA, Gash DM (2002) Chronic, controlled GDNF infusion promotes structural and functional recovery in advanced parkinsonian monkeys. Brain 125:2191–2201

    Article  PubMed  Google Scholar 

  • Grunblatt E, Mandel S, Berkuzki T, Youdim MB (1999) Apomorphine protects against MPTP-induced neurotoxicity in mice. Mov Disord 14:612–618

    Article  PubMed  CAS  Google Scholar 

  • Hamani C, Lozano AM (2003) Physiology and pathophysiology of Parkinson’s disease. Ann N Y Acad Sci 991:15–21

    Article  PubMed  Google Scholar 

  • Howard K (2003) First Parkinson gene therapy trial launches. Nat Biotechnol 21:1117–1118

    Article  PubMed  CAS  Google Scholar 

  • Hsich G, Sena-Esteves M, Breakefield XO (2002) Critical issues in gene therapy for neurologic disease. Hum Gene Ther 13:579–604

    Article  PubMed  CAS  Google Scholar 

  • Hsu LJ, Mallory M, Xia Y, Veinbergs I, Hashimoto M, Yoshimoto M, Thal LJ, Saitoh T, Masliah E (1998) Expression pattern of synucleins (non-Abeta component of Alzheimer’s disease amyloid precursor protein/alpha-synuclein) during murine brain development. J Neurochem 71:338–344

    Article  PubMed  CAS  Google Scholar 

  • Huntington’s Study Group, T (2001) A randomized, placebo-controlled trial of coenzyme Q 10, remacemide in Huntington’s disease. Neurology 57:397–404

    Google Scholar 

  • Hurelbrink CB, Barker RA (2001) Prospects for the treatment of Parkinson’ disease using neurotrophic factors. Expert Opin Pharmacother 2:1531–1543

    Article  PubMed  CAS  Google Scholar 

  • Hurelbrink CB, Barker RA (2004) The potential of GDNF as a treatment for Parkinson’s disease. Exp Neurol 185:1–6

    Article  PubMed  CAS  Google Scholar 

  • Iravani MM, Costa S, Jackson MJ, Tel BC, Cannizzaro C, Pearce RK, Jenner P (2001) GDNF reverses priming for dyskinesia in MPTP-treated, L-DOPA-primed common marmosets. Eur J Neurosci 13:597–608

    Article  PubMed  CAS  Google Scholar 

  • Ischiropoulos H (2003) Oxidative modifications of alpha-synuclein. Ann N Y Acad Sci 991:93–100

    Article  PubMed  CAS  Google Scholar 

  • Iwai A, Masliah E, Yoshimoto M, Ge N, Flanagan L, de Silva HA, Kittel A, Saitoh T (1995) The precursor protein of non-A beta component of Alzheimer’s disease amyloid is a presynaptic protein of the central nervous system. Neuron 14:467–475

    Article  PubMed  CAS  Google Scholar 

  • Jakes R, Spillantini MG, Goedert M (1994) Identification of two distinct synucleins from human brain. FEBS Lett 345:27–32

    Article  PubMed  CAS  Google Scholar 

  • Jenner P (2002) Pharmacology of dopamine agonists in the treatment of Parkinson’s disease. Neurology 58: S1–8

    PubMed  CAS  Google Scholar 

  • Kagan V, Serbinova E, Packer L (1990) Antioxidant effects of ubiquinones in microsomes and mitochondria are mediated by tocopherol recycling. Biochem Biophys Res Commun 169:851–857

    Article  PubMed  CAS  Google Scholar 

  • Kalia SK, Nash JE, Lozano AM (2004) To serve and protect? Interventions in the subthalamic nucleus for Parkinson’s disease. Commentary on “Ablation of the subthalamic nucleus protects dopaminergic phenotype but not cell survival in a rat model of Parkinson’s disease”. Exp Neurol 185:201–203

    Article  PubMed  Google Scholar 

  • Kingsman SM (2003) Lentivirus: a vector for nervous system applications. Ernst Schering Res Found Workshop: 179–207

    Google Scholar 

  • Kirik D, Rosenblad C, Bjorklund A (2000a) Preservation of a functional nigrostriatal dopamine pathway by GDNF in the intrastriatal 6-OHDA lesion model depends on the site of administration of the trophic factor. Eur J Neurosci 12:3871–3882

    Article  PubMed  CAS  Google Scholar 

  • Kirik D, Rosenblad C, Bjorklund A, Mandel RJ (2000b) Long-term rAAV-mediated gene transfer of GDNF in the rat Parkinson’s model: intrastriatal but not intranigral transduction promotes functional regeneration in the lesioned nigrostriatal system. J Neurosci 20:4686–4700

    PubMed  CAS  Google Scholar 

  • Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:605–608

    Article  PubMed  CAS  Google Scholar 

  • Kitamura Y, Kohno Y, Nakazawa M, Nomura Y (1997) Inhibitory effects of talipexole and pramipexole on MPTP-induced dopamine reduction in the striatum of C57BL/6 N mice. Jpn J Pharmacol 74:51–57

    PubMed  CAS  Google Scholar 

  • Kitamura Y, Kosaka T, Kakimura JI, Matsuoka Y, Kohno Y, Nomura Y, Taniguchi T (1998) Protective effects of the antiparkinsonian drugs talipexole and pramipexole against 1-methyl-4-phenylpyridinium-induced apoptotic death in human neuroblastoma SH-SY5Y cells. Mol Pharmacol 54:1046–1054

    PubMed  CAS  Google Scholar 

  • Kordower JH (2003) In vivo gene delivery of glial cell line-derived neurotrophic factor for Parkinson’s disease. Ann Neurol 53Suppl 3:S120–132; discussion S132–134

    Article  PubMed  CAS  Google Scholar 

  • Kordower JH, Emborg ME, Bloch J, Ma SY, Chu Y, Leventhal L, McBride J, Chen EY, Palfi S, Roitberg BZ, Brown WD, Holden JE, Pyzalski R, Taylor MD, Carvey P, Ling Z, Trono D, Hantraye P, Deglon N, Aebischer P (2000) Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson’s disease. Science 290:767–773

    Article  PubMed  CAS  Google Scholar 

  • Koroshetz WJ, Jenkins BG, Rosen BR, Beal MF (1997) Energy metabolism defects in Huntington’s disease and effects of coenzyme Q10. Ann Neurol 41:160–165

    Article  PubMed  CAS  Google Scholar 

  • Krack P, Benazzouz A, Pollak P, Limousin P, Piallat B, Hoffmann D, Xie J, Benabid AL (1998) Treatment of tremor in Parkinson’s disease by subthalamic nucleus stimulation. Mov Disord 13:907–914

    Article  PubMed  CAS  Google Scholar 

  • Kruger R, Kuhn W, Muller T, Woitalla D, Graeber M, Kosel S, Przuntek H, Epplen JT, Schols L, Riess O (1998) Ala30Promutation in the gene encoding alpha-synuclein in Parkinson’s disease. Nat Genet 18:106–108

    Article  PubMed  CAS  Google Scholar 

  • Kurlan R (2003) Declining medication requirement in some patients with advanced Parkinson disease and dementia. Clin Neuropharmacol 26:171

    Article  PubMed  Google Scholar 

  • Lecerf JM, Shirley TL, Zhu Q, Kazantsev A, Amersdorfer P, Housman DE, Messer A, Huston JS (2001) Human single-chain Fv intrabodies counteract in situ huntingtin aggregation in cellular models of Huntington’s disease. Proc Natl Acad Sci 98:4764–4769

    Article  PubMed  CAS  Google Scholar 

  • Lee EA, Lee WY, Kim YS, Kang UJ (2003) The effects of chronic L-DOPA therapy on pharmacodynamic parameters in a rat model of motor response fluctuations. Exp Neurol 184:304–12

    Article  PubMed  CAS  Google Scholar 

  • Lee FJ, Liu F, Pristupa ZB, Niznik HB (2001) Direct binding and functional coupling of alpha-synuclein to the dopamine transporters accelerate dopamine-induced apoptosis. FASEB J 15:916–926

    Article  PubMed  CAS  Google Scholar 

  • Li J, Zhu M, Manning-Bog AB, Di Monte DA, Fink AL (2004) Dopamine and L-dopa disaggregate amyloid fibrils: implications for Parkinson’s and Alzheimer’s disease. FASEB J 18:962–964

    Article  PubMed  CAS  Google Scholar 

  • Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F (1993) GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260:1130–1132

    Article  PubMed  CAS  Google Scholar 

  • Lindner MD, Winn SR, Baetge EE, Hammang JP, Gentile FT, Doherty E, Mc-Dermott PE, Frydel B, Ullman MD, Schallert T, et al. (1995) Implantation of encapsulated catecholamine and GDNF-producing cells in rats with unilateral dopamine depletions and parkinsonian symptoms. Exp Neurol 132:62–76

    Article  PubMed  CAS  Google Scholar 

  • Maguire-Zeiss KA, Federoff HJ (2003) Convergent pathobiologic model of Parkinson’s disease. Ann N Y Acad Sci 991:152–166

    Article  PubMed  CAS  Google Scholar 

  • Malone J, Sullivan MA (1996) Analysis of antibody selection by phage display utilizing anti-phenobarbital antibodies. J Mol Recognit 9:738–745

    Article  PubMed  CAS  Google Scholar 

  • Mann DM, Jones D, Prinja D, Purkiss MS (1990) The prevalence of amyloid (A4) protein deposits within the cerebral and cerebellar cortex in Down’s syndrome and Alzheimer’s disease. Acta Neuropathol (Berl) 80:318–327

    Article  PubMed  CAS  Google Scholar 

  • Marco S, Canudas AM, Canals JM, Gavalda N, Perez-Navarro E, Alberch J (2002) Excitatory amino acids differentially regulate the expression of GDNF, neurturin, and their receptors in the adult rat striatum. Exp Neurol 174:243–252

    Article  PubMed  CAS  Google Scholar 

  • Maroteaux L, Campanelli JT, Scheller RH (1988) Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci 8:2804–2815

    PubMed  CAS  Google Scholar 

  • Matthews RT, Yang L, Jenkins BG, Ferrante RJ, Rosen BR, Kaddurah-Daouk R, Beal MF (1998) Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington’s disease. J Neurosci 18:156–163

    PubMed  CAS  Google Scholar 

  • Mizuno Y, Shimoda-Matsubayashi S, Matsumine H, Morikawa N, Hattori N, Kondo T (1999) Genetic and environmental factors in the pathogenesis of Parkinson’s disease. Adv Neurol 80:171–179

    PubMed  CAS  Google Scholar 

  • Mochizuki H, Mizuno Y (2003) Gene therapy for Parkinson’s disease. J Neural Transm Suppl: 205–213

    Google Scholar 

  • Morelli M (2003) Adenosine A2A antagonists: potential preventive and palliative treatment for Parkinson’s disease. Exp Neurol 184:20–23

    Article  PubMed  CAS  Google Scholar 

  • Muralikrishnan D, Mohanakumar KP (1998) Neuroprotection by bromocriptine against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice. FASEB J 12:905–912

    PubMed  CAS  Google Scholar 

  • Murphy RC, Messer A (2004) A single-chain Fv intrabody provides functional protection against the effects of mutant protein in an organotypic slice culture model of Huntington’s disease. Brain Res Mol Brain Res 121:141–145

    Article  PubMed  CAS  Google Scholar 

  • Nakao N, Yokote H, Nakai K, Itakura T (2000) Promotion of survival and regeneration of nigral dopamine neurons in a rat model of Parkinson’s disease after implantation of embryonal carcinoma-derived neurons genetically engineered to produce glial cell line-derived neurotrophic factor. J Neurosurg 92:659–670

    Article  PubMed  CAS  Google Scholar 

  • Nutt JG (2003) Long-term L-DOPA therapy: challenges to our understanding and for the care of people with Parkinson’s disease. Exp Neurol 184:9–13

    Article  PubMed  CAS  Google Scholar 

  • Ogawa N, Tanaka K, Asanuma M, Kawai M, Masumizu T, Kohno M, Mori A (1994) Bromocriptine protects mice against 6-hydroxydopamine and scavenges hydroxyl free radicals in vitro. Brain Res 657:207–213

    Article  PubMed  CAS  Google Scholar 

  • Ogomori K, Kitamoto T, Tateishi J, Sato Y, Suetsugu M, Abe M (1989) Betaprotein amyloid is widely distributed in the central nervous system of patients with Alzheimer’s disease. Am J Pathol 134:243–251

    PubMed  CAS  Google Scholar 

  • Olanow CW, Tatton WG (1999) Etiology and pathogenesis of Parkinson’s disease. Annu Rev Neurosci 22:123–144

    Article  PubMed  CAS  Google Scholar 

  • Olanow CW, Watts RL, Koller WC (2001) An algorithm (decision tree) for the management of Parkinson’s disease (2001): treatment guidelines. Neurology 56: S1–S88

    PubMed  CAS  Google Scholar 

  • Opacka-Juffry J, Ashworth S, Hume SP, Martin D, Brooks DJ, Blunt SB (1995) GDNF protects against 6-OHDA nigrostriatal lesion: in vivo study with microdialysis and PET. Neuroreport 7:348–352

    PubMed  CAS  Google Scholar 

  • Oransky I (2003) Gene therapy trial for Parkinson’s disease begins. Lancet 362:712

    Article  PubMed  Google Scholar 

  • Parkinson J (1817) An essay on the shaking palsy. London

    Google Scholar 

  • Perrin RJ, Woods WS, Clayton DF, George JM (2000) Interaction of human alpha-Synuclein and Parkinson’s disease variants with phospholipids. Structural analysis using site-directed mutagenesis. J Biol Chem 275:34393–34398

    Article  PubMed  CAS  Google Scholar 

  • Polymeropoulos MH (2000) Genetics of Parkinson’s disease. Ann N Y Acad Sci 920:28–32

    Article  PubMed  CAS  Google Scholar 

  • 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 274:1197–1199

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Przedborski S, Jackson-Lewis V, Naini AB, Jakowec M, Petzinger G, Miller R, Akram M (2001) The parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a technical review of its utility and safety. J Neurochem 76:1265–1274

    Article  PubMed  CAS  Google Scholar 

  • Rochet JC, Outeiro TF, Conway KA, Ding TT, Volles MJ, Lashuel HA, Bieganski RM, Lindquist SL, Lansbury PT (2004) Interactions among alphasynuclein, dopamine, and biomembranes: some clues for understanding neurodegeneration in Parkinson’s disease. J Mol Neurosci 23:23–34

    Article  PubMed  CAS  Google Scholar 

  • Sariola H, Saarma M (2003) Novel functions and signalling pathways for GDNF. J Cell Sci 116:3855–3862

    Article  PubMed  CAS  Google Scholar 

  • Schapira AH, Olanow CW (2003) Rationale for the use of dopamine agonists as neuroprotective agents in Parkinson’s disease. Ann Neurol 53Suppl 3:S149–157; discussion S157–159

    Article  PubMed  CAS  Google Scholar 

  • Scherfler C, Khan NL, Pavese N, Eunson L, Graham E, Lees AJ, Quinn NP, Wood NW, Brooks DJ, Piccini PP (2004) Striatal and cortical pre-and postsynaptic dopaminergic dysfunction in sporadic parkin-linked parkinsonism. Brain 127 (Pt 6):1332–1342

    Article  PubMed  Google Scholar 

  • Sebastiao AM, Ribeiro JA (2000) Fine-tuning neuromodulation by adenosine. Trends Pharmacol Sci 21:341–346

    Article  PubMed  CAS  Google Scholar 

  • Seidler A, Hellenbrand W, Robra BP, Vieregge P, Nischan P, Joerg J, Oertel WH, Ulm G, Schneider E (1996) Possible environmental, occupational, and other etiologic factors for Parkinson’s disease: a case-control study in Germany. Neurology 46:1275–1284

    PubMed  CAS  Google Scholar 

  • Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M (2002) Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 59:1541–1550

    Article  PubMed  Google Scholar 

  • Singleton A, Gwinn-Hardy K, Sharabi Y, Li ST, Holmes C, Dendi R, Hardy J, Crawley A, Goldstein DS (2004) Association between cardiac denervation and parkinsonism caused by alpha-synuclein gene triplication. Brain 127:768–772

    Article  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  PubMed  CAS  Google Scholar 

  • Song DD, Shults CW, Sisk A, Rockenstein E, Masliah E (2004) Enhanced substantia nigra mitochondrial pathology in human alpha-synuclein transgenic mice after treatment with MPTP. Exp Neurol 186:158–172

    Article  PubMed  CAS  Google Scholar 

  • Stocchi F (2003) Prevention and treatment of motor fluctuations. Parkinsonism Relat Disord 9Suppl 2:S73–81

    Article  PubMed  Google Scholar 

  • Suenaga T, Hirano A, Llena JF, Ksiezak-Reding H, Yen SH, Dickson DW (1990) Modified Bielschowsky and immunocytochemical studies on cerebellar plaques in Alzheimer’s disease. J Neuropathol Exp Neurol 49:31–40

    PubMed  CAS  Google Scholar 

  • Svenningsson P, Nomikos GG, Ongini E, Fredholm BB (1997) Antagonism of adenosine A2A receptors underlies the behavioural activating effect of caffeine and is associated with reduced expression of messenger RNA for NGFI-A and NGFI-B in caudate-putamen and nucleus accumbens. Neuroscience 79:753–764

    Article  PubMed  CAS  Google Scholar 

  • Takashima H, Tsujihata M, Kishikawa M, Freed WJ (1999) Bromocriptine protects dopaminergic neurons from levodopa-induced toxicity by stimulating D(2)receptors. Exp Neurol 159:98–104

    Article  PubMed  CAS  Google Scholar 

  • Takenouchi T, Hashimoto M, Hsu LJ, Mackowski B, Rockenstein E, Mallory M, Masliah E (2001) Reduced neuritic outgrowth and cell adhesion in neuronal cells transfected with human alpha-synuclein. Mol Cell Neurosci 17:141–150

    Article  PubMed  CAS  Google Scholar 

  • Tarnopolsky MA, Beal MF (2001) Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Ann Neurol 49:561–574

    Article  PubMed  CAS  Google Scholar 

  • Thiruchelvam M, Brockel BJ, Richfield EK, Baggs RB, Cory-Slechta DA (2000a) Potentiated and preferential effects of combined paraquat and maneb on nigrostriatal dopamine systems: environmental risk factors for Parkinson’s disease? Brain Res 873:225–234

    Article  PubMed  CAS  Google Scholar 

  • Thiruchelvam M, Richfield EK, Baggs RB, Tank AW, Cory-Slechta DA (2000b) The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: implications for Parkinson’s disease. J Neurosci 20:9207–9214

    PubMed  CAS  Google Scholar 

  • Thiruchelvam M, Richfield EK, Goodman BM, Baggs RB, Cory-Slechta DA (2002) Developmental exposure to the pesticides paraquat and maneb and the Parkinson’s disease phenotype. Neurotoxicology 23:621–633

    Article  PubMed  CAS  Google Scholar 

  • Tomac A, Lindqvist E, Lin LF, Ogren SO, Young D, Hoffer BJ, Olson L (1995) Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 373:335–339

    Article  PubMed  CAS  Google Scholar 

  • Vigna E, Cavalieri S, Ailles L, Geuna M, Loew R, Bujard H, Naldini L (2002) Robust and efficient regulation of transgene expression in vivo by improved tetracycline-dependent lentiviral vectors. Mol Ther 5:252–261

    Article  PubMed  CAS  Google Scholar 

  • Vu TQ, Ling ZD, Ma SY, Robie HC, Tong CW, Chen EY, Lipton JW, Carvey PM (2000) Pramipexole attenuates the dopaminergic cell loss induced by intraventricular 6-hydroxydopamine. J Neural Transm 107:159–176

    Article  PubMed  CAS  Google Scholar 

  • Warner TT, Schapira AH (2003) Genetic and environmental factors in the cause of Parkinson’s disease. Ann Neurol 53Suppl 3:S16–23; discussion S23–25

    Article  PubMed  CAS  Google Scholar 

  • Weinreb PH, Zhen W, Poon AW, Conway KA, Lansbury, PT Jr. (1996) NACP, a protein implicated in Alzheimer’s disease and learning, is natively unfolded. Biochemistry 35:13709–13815

    Article  PubMed  CAS  Google Scholar 

  • Whone, AL, Moore RY, Piccini PP, Brooks DJ (2003) Plasticity of the nigropallidal pathway in Parkinson’s disease. Ann Neurol 53:206–213

    Article  PubMed  Google Scholar 

  • Zou L, Jankovic J, Rowe DB, Xie W, Appel SH, Le W (1999) Neuroprotection by pramipexole against dopamine-and levodopa-induced cytotoxicity. Life Sci 64:1275–1285

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Maguire-Zeiss, K.A., Federoff, H.J. (2005). Novel Gene Therapeutic Strategies for Neurodegenerative Diseases. In: Perez, H.D., Mitrovic, B., Baron Van Evercooren, A. (eds) Opportunities and Challenges of the Therapies Targeting CNS Regeneration. Ernst Schering Research Foundation Workshop, vol 53. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-27626-2_9

Download citation

Publish with us

Policies and ethics