1 Caughey, B. & Lansbury, P. T. Protofibrils, pores, fibrils, and neurodegeneration:
separating the responsible protein aggregates from the innocent bystanders. Annu Rev Neurosci 26, 267-298, doi:10.1146/annurev.neuro.26.010302.081142 (2003).
2 Jankowsky, J. L. et al. Transgenic mouse models of neurodegenerative disease:
opportunities for therapeutic development. Current neurology and neuroscience reports 2, 457-464 (2002).
3 Kerksiek, K. Infektionen und neurodegenerative Erkrankungen: Prionen und mehr.
(2009).
4 Skovronsky, D. M., Lee, V. M. & Trojanowski, J. Q. Neurodegenerative diseases:
new concepts of pathogenesis and their therapeutic implications. Annual review of pathology 1, 151-170, doi:10.1146/annurev.pathol.1.110304.100113 (2006).
5 Kretzschmar, H. A. & Neumann, M. [Neuropathological diagnosis of neurodegenerative and dementia diseases]. Der Pathologe 21, 364-374 (2000).
6 Alzheimer, A. Über eine eigenartige Hirnerkrankung. Allgemeine Zeitschrift für Psychiatrie 64, 146-148 (1907).
7 Maurer, K. Alzheimer: Das Leben eines Arztes und die Karriere einer Krankheit.
Vol. 2 (Piper, 1998).
8 Prince, M. World Alzheimer Report (Alzheimer's Disease International, 2009).
9 Bickel, H. Die Epidemiologie der Demenz. (Deutsche Alzheimer Gesellschaft, 2010).
10 Selkoe, D. J. Translating cell biology into therapeutic advances in Alzheimer's disease. Nature 399, A23-31 (1999).
11 Lautenschlager, N., Kurz, A. & Muller, U. [Inheritable causes and risk factors of Alzheimer's disease]. Der Nervenarzt 70, 195-205 (1999).
12 Ballard, C. et al. Alzheimer's disease. Lancet 377, 1019-1031, doi:10.1016/S0140-6736(10)61349-9 (2011).
13 LaFerla, F. M., Green, K. N. & Oddo, S. Intracellular amyloid-beta in Alzheimer's disease. Nature reviews. Neuroscience 8, 499-509, doi:10.1038/nrn2168 (2007).
14 Krämer, G. Alzheimer Krankheit: Ursachen, Krankheitszeichen, Untersuchung, Behandlung. Vol. 2 (TRIAS-Thieme Hippokrates Enke Stuttgart, 1993).
100 LITERATURVERZEICHNIS
15 Hardy, J. & Selkoe, D. J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353-356, doi:10.1126/science.1072994 (2002).
16 Braak, H. et al. Pattern of brain destruction in Parkinson's and Alzheimer's diseases.
J Neural Transm 103, 455-490 (1996).
17 Mandelkow, E. M. & Mandelkow, E. Tau in Alzheimer's disease. Trends in cell biology 8, 425-427 (1998).
18 Friedhoff, P., von Bergen, M., Mandelkow, E. M. & Mandelkow, E. Structure of tau protein and assembly into paired helical filaments. Biochim Biophys Acta 1502, 122-132 (2000).
19 Fischer, A. Advances in Alzheimer's and Parkinson's Disease. (Springer, 2008).
20 Bondareff, W., Harrington, C. R., McDaniel, S. W., Wischik, C. M. & Roth, M.
Presence of axonal paired helical filament-tau in Alzheimer's disease:
submicroscopic localization. J Neurosci Res 38, 664-669, doi:10.1002/jnr.490380609 (1994).
21 Pantel, J. Zerebrale Korrelate klinischer und neuropsychologischer Veränderungen in den Verlaufsstadien der Alzheimer-Demenz. Untersuchungen mit der quantitativen Magnetresonanztomographie. Monographien aus dem Gesamtgebiet der Psychiatrie.
(Steinkopf, 2006).
22 Crowther, R. A. & Goedert, M. Abnormal tau-containing filaments in neurodegenerative diseases. J Struct Biol 130, 271-279, doi:10.1006/jsbi.2000.4270 (2000).
23 Selkoe, D. J. Alzheimer's disease: genes, proteins, and therapy. Physiological reviews 81, 741-766 (2001).
24 Blennow, K., de Leon, M. J. & Zetterberg, H. Alzheimer's disease. Lancet 368, 387-403, doi:10.1016/S0140-6736(06)69113-7 (2006).
25 Cárdenas-Aguayo, M. d. C. et al. in Neurochemistry (ed Dr. Thomas Heinbockel) 414 (InTech, 2014).
26 Deane, R., Bell, R. D., Sagare, A. & Zlokovic, B. V. Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer's disease. CNS & neurological disorders drug targets 8, 16-30 (2009).
27 Suh, Y. H. & Checler, F. Amyloid precursor protein, presenilins, and alpha-synuclein: molecular pathogenesis and pharmacological applications in Alzheimer's disease. Pharmacological reviews 54, 469-525 (2002).
LITERATURVERZEICHNIS 101
28 Haass, C. & Selkoe, D. J. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol 8, 101-112, doi:10.1038/nrm2101 (2007).
29 Citron, M. Strategies for disease modification in Alzheimer's disease. Nature reviews. Neuroscience 5, 677-685, doi:10.1038/nrn1495 (2004).
30 Huse, J. T. & Doms, R. W. Neurotoxic traffic: uncovering the mechanics of amyloid production in Alzheimer's disease. Traffic 2, 75-81 (2001).
31 Naslund, J. et al. Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline. JAMA : the journal of the American Medical Association 283, 1571-1577 (2000).
32 Wang, J., Dickson, D. W., Trojanowski, J. Q. & Lee, V. M. The levels of soluble versus insoluble brain Abeta distinguish Alzheimer's disease from normal and pathologic aging. Exp Neurol 158, 328-337, doi:10.1006/exnr.1999.7085 (1999).
33 Gasser, T. et al. Genetic linkage studies in autosomal dominant parkinsonism:
evaluation of seven candidate genes. Ann Neurol 36, 387-396, doi:10.1002/ana.410360310 (1994).
34 Adams, R. D., Victor, M. & Ropper, A. H. Principles of neurology. 6th edn, (McGraw-Hill, Health Professions Division, 1997).
35 Sinje, S. Untersuchung der Plasmaoxidierbarkeit und des Antioxidantienstatus im Blutplasma von Patienten mit Morbus Parkinson:ein Beitrag zur Frage des oxidativen Streß in der Pathogenese des Morbus Parkinson, Universität Hamburg, (2000).
36 Albin, R. L., Young, A. B. & Penney, J. B. The functional anatomy of basal ganglia disorders. Trends in neurosciences 12, 366-375 (1989).
37 Fearnley, J. M. & Lees, A. J. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain : a journal of neurology 114 ( Pt 5), 2283-2301 (1991).
38 Gibb, W. R. & Lees, A. J. Anatomy, pigmentation, ventral and dorsal subpopulations of the substantia nigra, and differential cell death in Parkinson's disease. Journal of neurology, neurosurgery, and psychiatry 54, 388-396 (1991).
39 Lotharius, J. & Brundin, P. Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein. Nature reviews. Neuroscience 3, 932-942, doi:10.1038/nrn983 (2002).
40 Goedert, M. Alpha-synuclein and neurodegenerative diseases. Nature reviews.
Neuroscience 2, 492-501, doi:10.1038/35081564 (2001).
102 LITERATURVERZEICHNIS
41 Auluck, P. K., Caraveo, G. & Lindquist, S. alpha-Synuclein: membrane interactions and toxicity in Parkinson's disease. Annual review of cell and developmental biology 26, 211-233, doi:10.1146/annurev.cellbio.042308.113313 (2010).
42 Weinreb, P. H., Zhen, W., Poon, A. W., Conway, K. A. & Lansbury, P. T., Jr.
NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded.
Biochemistry 35, 13709-13715, doi:10.1021/bi961799n (1996).
43 Clayton, D. F. & George, J. M. The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease. Trends in neurosciences 21, 249-254 (1998).
44 Davidson, W. S., Jonas, A., Clayton, D. F. & George, J. M. Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J Biol Chem 273, 9443-9449 (1998).
45 Conway, K. A., Harper, J. D. & Lansbury, P. T., Jr. Fibrils formed in vitro from alpha-synuclein and two mutant forms linked to Parkinson's disease are typical amyloid. Biochemistry 39, 2552-2563 (2000).
46 Conway, K. A. et al. Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease:
implications for pathogenesis and therapy. Proc Natl Acad Sci U S A 97, 571-576 (2000).
47 Dauer, W. & Przedborski, S. Parkinson's disease: mechanisms and models. Neuron 39, 889-909 (2003).
48 Seidler, A. et al. Possible environmental, occupational, and other etiologic factors for Parkinson's disease: a case-control study in Germany. Neurology 46, 1275-1284 (1996).
49 Cannon, J. R. & Greenamyre, J. T. Gene-environment interactions in Parkinson's disease: Specific evidence in humans and mammalian models. Neurobiol Dis, doi:10.1016/j.nbd.2012.06.025 (2012).
50 Dexter, D. T. et al. Increased levels of lipid hydroperoxides in the parkinsonian substantia nigra: an HPLC and ESR study. Mov Disord 9, 92-97, doi:10.1002/mds.870090115 (1994).
51 Jenner, P., Dexter, D. T., Sian, J., Schapira, A. H. & Marsden, C. D. Oxidative stress as a cause of nigral cell death in Parkinson's disease and incidental Lewy body disease. The Royal Kings and Queens Parkinson's Disease Research Group. Ann Neurol 32 Suppl, S82-87 (1992).
52 Fowler, C. J., Wiberg, A., Oreland, L., Marcusson, J. & Winblad, B. The effect of age on the activity and molecular properties of human brain monoamine oxidase. J Neural Transm 49, 1-20 (1980).
LITERATURVERZEICHNIS 103
53 Spina, M. B. & Cohen, G. Dopamine turnover and glutathione oxidation:
implications for Parkinson disease. Proc Natl Acad Sci U S A 86, 1398-1400 (1989).
54 Wexler, N. S. et al. Homozygotes for Huntington's disease. Nature 326, 194-197, doi:10.1038/326194a0 (1987).
55 Barron, L. H. et al. A study of the Huntington's disease associated trinucleotide repeat in the Scottish population. Journal of medical genetics 30, 1003-1007 (1993).
56 Arrasate, M. & Finkbeiner, S. Protein aggregates in Huntington's disease. Exp Neurol, doi:10.1016/j.expneurol.2011.12.013 (2011).
57 Brooks, S. P., Jones, L. & Dunnett, S. B. Comparative analysis of pathology and behavioural phenotypes in mouse models of Huntington's disease. Brain research bulletin 88, 81-93, doi:10.1016/j.brainresbull.2011.10.002 (2012).
58 Dexter, D., Moye-Rowley, W. S., Wu, A. L. & Golin, J. Mutations in the yeast PDR3, PDR4, PDR7 and PDR9 pleiotropic (multiple) drug resistance loci affect the transcript level of an ATP binding cassette transporter encoding gene, PDR5.
Genetics 136, 505-515 (1994).
59 Zheng, Z. & Diamond, M. I. Huntington disease and the huntingtin protein. Prog Mol Biol Transl Sci 107, 189-214, doi:10.1016/B978-0-12-385883-2.00010-2 (2012).
60 Di Prospero, N. A. & Tagle, D. A. Normal and mutant huntingtin: partners in crime.
Nat Med 6, 1208-1209, doi:10.1038/81294 (2000).
61 Poeck, K. H., W. Neurologie. Vol. 12 (Springer Medizin Verlag 2006).
62 Di Carlo, M., Giacomazza, D. & San Biagio, P. L. Alzheimer's disease: biological aspects, therapeutic perspectives and diagnostic tools. Journal of physics. Condensed matter : an Institute of Physics journal 24, 244102, doi:10.1088/0953-8984/24/24/244102 (2012).
63 Dovey, H. F. et al. Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem 76, 173-181 (2001).
64 Beher, D. et al. Selected non-steroidal anti-inflammatory drugs and their derivatives target gamma-secretase at a novel site. Evidence for an allosteric mechanism. J Biol Chem 279, 43419-43426, doi:10.1074/jbc.M404937200 (2004).
65 Phiel, C. J., Wilson, C. A., Lee, V. M. & Klein, P. S. GSK-3alpha regulates production of Alzheimer's disease amyloid-beta peptides. Nature 423, 435-439, doi:10.1038/nature01640 (2003).
66 Netzer, W. J. et al. Gleevec inhibits beta-amyloid production but not Notch cleavage.
Proc Natl Acad Sci U S A 100, 12444-12449, doi:10.1073/pnas.1534745100 (2003).
104 LITERATURVERZEICHNIS
67 Best, J. D. et al. The novel gamma secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1-trifl
uoromethanesulfonamide (MRK-560) reduces amyloid plaque deposition without evidence of notch-related pathology in the Tg2576 mouse. The Journal of pharmacology and experimental therapeutics 320, 552-558, doi:10.1124/jpet.106.114330 (2007).
68 Eriksen, J. L. et al. NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. The Journal of clinical investigation 112, 440-449, doi:10.1172/JCI18162 (2003).
69 Cole, D. C. et al. Acylguanidines as small-molecule beta-secretase inhibitors.
Journal of medicinal chemistry 49, 6158-6161, doi:10.1021/jm0607451 (2006).
70 Hanessian, S. et al. Structure-based design, synthesis, and memapsin 2 (BACE) inhibitory activity of carbocyclic and heterocyclic peptidomimetics. Journal of medicinal chemistry 48, 5175-5190, doi:10.1021/jm050142+ (2005).
71 Gao, C., Holscher, C., Liu, Y. & Li, L. GSK3: a key target for the development of novel treatments for type 2 diabetes mellitus and Alzheimer disease. Reviews in the neurosciences 23, 1-11, doi:10.1515/rns.2011.061 (2012).
72 Sereno, L. et al. A novel GSK-3beta inhibitor reduces Alzheimer's pathology and rescues neuronal loss in vivo. Neurobiol Dis 35, 359-367, doi:10.1016/j.nbd.2009.05.025 (2009).
73 Pekary, A. E., Sattin, A. & Blood, J. Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by leptin. Brain Res 1345, 9-18, doi:10.1016/j.brainres.2010.05.039 (2010).
74 Inglis, K. J. et al. Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system. J Biol Chem 284, 2598-2602, doi:10.1074/jbc.C800206200 (2009).
75 Chico, L. K., Van Eldik, L. J. & Watterson, D. M. Targeting protein kinases in central nervous system disorders. Nature reviews. Drug discovery 8, 892-909, doi:10.1038/nrd2999 (2009).
76 Lee, K. W. et al. Enhanced phosphatase activity attenuates alpha-synucleinopathy in a mouse model. J Neurosci 31, 6963-6971, doi:10.1523/JNEUROSCI.6513-10.2011 (2011).
77 Auger, R. R. & Boeve, B. F. Sleep disorders in neurodegenerative diseases other than Parkinson's disease. Handbook of clinical neurology / edited by P.J. Vinken and G.W.
Bruyn 99, 1011-1050, doi:10.1016/B978-0-444-52007-4.00020-5 (2011).
78 Feng, Y. & Wang, X. Antioxidant therapies for Alzheimer's disease. Oxidative medicine and cellular longevity 2012, 472932, doi:10.1155/2012/472932 (2012).
LITERATURVERZEICHNIS 105
79 Nunomura, A. et al. Involvement of oxidative stress in Alzheimer disease. J Neuropathol Exp Neurol 65, 631-641, doi:10.1097/01.jnen.0000228136.58062.bf (2006).
80 Prasanthi, J. R. et al. Caffeine protects against oxidative stress and Alzheimer's disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet.
Free radical biology & medicine 49, 1212-1220,
doi:10.1016/j.freeradbiomed.2010.07.007 (2010).
81 Rezai-Zadeh, K. et al. Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci 25, 8807-8814, doi:10.1523/JNEUROSCI.1521-05.2005 (2005).
82 Sun, A. Y., Wang, Q., Simonyi, A. & Sun, G. Y. Resveratrol as a therapeutic agent for neurodegenerative diseases. Molecular neurobiology 41, 375-383, doi:10.1007/s12035-010-8111-y (2010).
83 Ammon, H. P., Safayhi, H., Mack, T. & Sabieraj, J. Mechanism of antiinflammatory actions of curcumine and boswellic acids. Journal of ethnopharmacology 38, 113-119 (1993).
84 Lim, G. P. et al. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 21, 8370-8377 (2001).
85 Lohani, M. et al. Anti-oxidative and DNA protecting effects of flavonoids-rich Scutellaria lateriflora. Natural product communications 8, 1415-1418 (2013).
86 Zhang, Z., Lian, X. Y., Li, S. & Stringer, J. L. Characterization of chemical ingredients and anticonvulsant activity of American skullcap (Scutellaria lateriflora).
Phytomedicine 16, 485-493, doi:10.1016/j.phymed.2008.07.011 (2009).
87 Eiden, M., Leidel, F., Strohmeier, B., Fast, C. & Groschup, M. H. A Medicinal Herb Scutellaria lateriflora Inhibits PrP Replication in vitro and Delays the Onset of Prion Disease in Mice. Frontiers in psychiatry / Frontiers Research Foundation 3, 9, doi:10.3389/fpsyt.2012.00009 (2012).
88 Li, C., Lin, G. & Zuo, Z. Pharmacological effects and pharmacokinetics properties of Radix Scutellariae and its bioactive flavones. Biopharmaceutics & drug disposition 32, 427-445, doi:10.1002/bdd.771 (2011).
89 Srinivas, N. R. Baicalin, an emerging multi-therapeutic agent: pharmacodynamics, pharmacokinetics, and considerations from drug development perspectives.
Xenobiotica; the fate of foreign compounds in biological systems 40, 357-367, doi:10.3109/00498251003663724 (2010).
90 Gafner, S. et al. Inhibition of [3H]-LSD binding to 5-HT7 receptors by flavonoids from Scutellaria lateriflora. J Nat Prod 66, 535-537, doi:10.1021/np0205102 (2003).
106 LITERATURVERZEICHNIS
91 Awad, R. et al. Phytochemical and biological analysis of skullcap (Scutellaria lateriflora L.): a medicinal plant with anxiolytic properties. Phytomedicine 10, 640-649, doi:10.1078/0944-7113-00374 (2003).
92 Cheng, F. et al. Baicalin's Therapeutic Time Window of Neuroprotection during Transient Focal Cerebral Ischemia and Its Antioxidative Effects In Vitro and In Vivo.
Evidence-based complementary and alternative medicine : eCAM 2013, 120261, doi:10.1155/2013/120261 (2013).
93 Lee, H. H. et al. Differential effects of natural polyphenols on neuronal survival in primary cultured central neurons against glutamate- and glucose deprivation-induced neuronal death. Brain Res 986, 103-113 (2003).
94 Lee, E., Park, H. R., Ji, S. T., Lee, Y. & Lee, J. Baicalein Attenuates Astroglial Activation in the 1-Methyl-4-Phenyl-1,2,3, 4-Tetrahydropyridine-Induced Parkinson's Disease Model by Downregulating the Activations of Nuclear Factor-kappa B, ERK, and JNK. J Neurosci Res 92, 130-139, doi:Doi 10.1002/Jnr.23307 (2014).
95 Saper, C. B., Wainer, B. H. & German, D. C. Axonal and transneuronal transport in the transmission of neurological disease: potential role in system degenerations, including Alzheimer's disease. Neuroscience 23, 389-398 (1987).
96 Hardy, J. et al. Transmitter deficits in Alzheimer's disease. Neurochemistry international 7, 545-563 (1985).
97 Nilsson, S. F. & Peterson, P. A. Evidence for multiple thyroxine-binding sites in human prealbumin. J Biol Chem 246, 6098-6105 (1971).
98 Schwarzman, A. L. et al. Transthyretin sequesters amyloid beta protein and prevents amyloid formation. Proc Natl Acad Sci U S A 91, 8368-8372 (1994).
99 Costa, R., Goncalves, A., Saraiva, M. J. & Cardoso, I. Transthyretin binding to A-Beta peptide--impact on A-A-Beta fibrillogenesis and toxicity. FEBS Lett 582, 936-942, doi:10.1016/j.febslet.2008.02.034 (2008).
100 Costa, R., Ferreira-da-Silva, F., Saraiva, M. J. & Cardoso, I. Transthyretin protects against A-beta peptide toxicity by proteolytic cleavage of the peptide: a mechanism sensitive to the Kunitz protease inhibitor. PLoS One 3, e2899, doi:10.1371/journal.pone.0002899 (2008).
101 Ribeiro, C. A., Saraiva, M. J. & Cardoso, I. Stability of the transthyretin molecule as a key factor in the interaction with a-beta peptide--relevance in Alzheimer's disease.
PLoS One 7, e45368, doi:10.1371/journal.pone.0045368 (2012).
102 Azevedo, A. C. et al. Clinical and biochemical study of 28 patients with mucopolysaccharidosis type VI. Clinical genetics 66, 208-213, doi:10.1111/j.1399-0004.2004.00277.x (2004).
LITERATURVERZEICHNIS 107
103 Bukau, B. & Horwich, A. L. The Hsp70 and Hsp60 chaperone machines. Cell 92, 351-366 (1998).
104 Klucken, J., Shin, Y., Masliah, E., Hyman, B. T. & McLean, P. J. Hsp70 Reduces alpha-Synuclein Aggregation and Toxicity. J Biol Chem 279, 25497-25502, doi:10.1074/jbc.M400255200 (2004).
105 Auluck, P. K., Meulener, M. C. & Bonini, N. M. Mechanisms of Suppression of {alpha}-Synuclein Neurotoxicity by Geldanamycin in Drosophila. J Biol Chem 280, 2873-2878, doi:10.1074/jbc.M412106200 (2005).
106 Westerheide, S. D. et al. Celastrols as inducers of the heat shock response and cytoprotection. J Biol Chem 279, 56053-56060, doi:10.1074/jbc.M409267200 (2004).
107 Cui, J. et al. Morphine protects against intracellular amyloid toxicity by inducing estradiol release and upregulation of Hsp70. J Neurosci 31, 16227-16240, doi:10.1523/JNEUROSCI.3915-11.2011 (2011).
108 Schenk, D. et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400, 173-177, doi:10.1038/22124 (1999).
109 Holmes, C. et al. Long-term effects of Abeta42 immunisation in Alzheimer's disease:
follow-up of a randomised, placebo-controlled phase I trial. Lancet 372, 216-223, doi:10.1016/S0140-6736(08)61075-2 (2008).
110 Delrieu, J., Ousset, P. J., Caillaud, C. & Vellas, B. 'Clinical trials in Alzheimer's disease': immunotherapy approaches. J Neurochem 120 Suppl 1, 186-193, doi:10.1111/j.1471-4159.2011.07458.x (2012).
111 Salloway, S. et al. A randomized, double-blind, placebo-controlled clinical trial of intravenous bapineuzumab in patients with mild to moderate Alzheimer's disease who are apolipoprotein E eta4 non-carriers. (European Federation of Neurological Societies, Stockholm, 2012).
112 Kuhnke, D. et al. MDR1-P-Glycoprotein (ABCB1) Mediates Transport of Alzheimer's amyloid-beta peptides--implications for the mechanisms of Abeta clearance at the blood-brain barrier. Brain Pathol 17, 347-353, doi:10.1111/j.1750-3639.2007.00075.x (2007).
113 Grimmer, T. et al. LRP-1 polymorphism is associated with global and regional amyloid load in Alzheimer's disease in humans in-vivo. NeuroImage. Clinical 4, 411-416, doi:10.1016/j.nicl.2014.01.016 (2014).
114 Castellano, J. M. et al. Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood Abeta clearance in a mouse model of beta-amyloidosis. Proc Natl Acad Sci U S A 109, 15502-15507, doi:10.1073/pnas.1206446109 (2012).
108 LITERATURVERZEICHNIS
115 Lam, F. C. et al. beta-Amyloid efflux mediated by p-glycoprotein. J Neurochem 76, 1121-1128 (2001).
116 Vogelgesang, S. et al. Deposition of Alzheimer's beta-amyloid is inversely correlated with P-glycoprotein expression in the brains of elderly non-demented humans.
Pharmacogenetics 12, 535-541 (2002).
117 Brenn, A. et al. St. John's Wort reduces beta-amyloid accumulation in a double transgenic Alzheimer's disease mouse model-role of P-glycoprotein. Brain Pathol 24, 18-24, doi:10.1111/bpa.12069 (2014).
118 Durr, D. et al. St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 68, 598-604, doi:10.1067/mcp.2000.112240 (2000).
119 Gutmann, H. et al. Hypericum perforatum: which constituents may induce intestinal MDR1 and CYP3A4 mRNA expression? Planta medica 72, 685-690, doi:10.1055/s-2006-931585 (2006).
120 Schwarz, U. I. et al. Induction of intestinal P-glycoprotein by St John's wort reduces the oral bioavailability of talinolol. Clin Pharmacol Ther 81, 669-678, doi:10.1038/sj.clpt.6100191 (2007).
121 Xie, H. R., Hu, L. S. & Li, G. Y. SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson's disease. Chinese medical journal 123, 1086-1092 (2010).
122 Avrahami, L. et al. Inhibition of Glycogen Synthase Kinase-3 Ameliorates beta-Amyloid Pathology and Restores Lysosomal Acidification and Mammalian Target of Rapamycin Activity in the Alzheimer Disease Mouse Model: IN VIVO AND IN VITRO STUDIES. J Biol Chem 288, 1295-1306, doi:10.1074/jbc.M112.409250 (2013).
123 Leidel, F. et al. Diphenylpyrazole-derived compounds increase survival time of mice after prion infection. Antimicrobial agents and chemotherapy 55, 4774-4781, doi:10.1128/AAC.00151-11 (2011).
124 Soto, C., Saborio, G. P. & Anderes, L. Cyclic amplification of protein misfolding:
application to prion-related disorders and beyond. Trends in neurosciences 25, 390-394 (2002).
125 Eiden, M. et al. Synergistic and strain-specific effects of bovine spongiform encephalopathy and scrapie prions in the cell-free conversion of recombinant prion protein. The Journal of general virology 87, 3753-3761, doi:10.1099/vir.0.81590-0 (2006).
126 Baskakov, I. V. The reconstitution of mammalian prion infectivity de novo. Febs J 274, 576-587, doi:10.1111/j.1742-4658.2007.05630.x (2007).
LITERATURVERZEICHNIS 109
127 Baskakov, I. V. et al. Self-assembly of recombinant prion protein of 106 residues.
Biochemistry 39, 2792-2804 (2000).
128 Baskakov, I. V., Legname, G., Baldwin, M. A., Prusiner, S. B. & Cohen, F. E.
Pathway complexity of prion protein assembly into amyloid. J Biol Chem 277, 21140-21148, doi:10.1074/jbc.M111402200 (2002).
129 Atarashi, R. et al. Simplified ultrasensitive prion detection by recombinant PrP conversion with shaking. Nature methods 5, 211-212, doi:10.1038/nmeth0308-211 (2008).
130 Ryou, C. & Mays, C. E. Prion propagation in vitro: are we there yet? International journal of medical sciences 5, 347-353 (2008).
131 Ding, Q., Markesbery, W. R., Chen, Q., Li, F. & Keller, J. N. Ribosome dysfunction is an early event in Alzheimer's disease. J Neurosci 25, 9171-9175, doi:10.1523/JNEUROSCI.3040-05.2005 (2005).
132 Kostka, M. et al. Single particle characterization of iron-induced pore-forming alpha-synuclein oligomers. J Biol Chem 283, 10992-11003, doi:10.1074/jbc.M709634200 (2008).
133 Tsigelny, I. F. et al. Mechanisms of hybrid oligomer formation in the pathogenesis of combined Alzheimer's and Parkinson's diseases. PLoS One 3, e3135, doi:10.1371/journal.pone.0003135 (2008).
134 Rockenstein, E., Crews, L. & Masliah, E. Transgenic animal models of neurodegenerative diseases and their application to treatment development. Advanced drug delivery reviews 59, 1093-1102, doi:10.1016/j.addr.2007.08.013 (2007).
135 Hattori, N. & Sato, S. Animal models of Parkinson's disease: Similarities and differences between the disease and models. Neuropathology 27, 479-483, doi:10.1111/j.1440-1789.2007.00842.x (2007).
136 Hall, A. M. & Roberson, E. D. Mouse models of Alzheimer's disease. Brain research bulletin 88, 3-12, doi:10.1016/j.brainresbull.2011.11.017 (2012).
137 Menalled, L. B. & Chesselet, M. F. Mouse models of Huntington's disease. Trends in pharmacological sciences 23, 32-39 (2002).
138 Feany, M. B. & Bender, W. W. A Drosophila model of Parkinson's disease. Nature 404, 394-398, doi:10.1038/35006074 (2000).
139 Shulman, J. M., Shulman, L. M., Weiner, W. J. & Feany, M. B. From fruit fly to bedside: translating lessons from Drosophila models of neurodegenerative disease.
Current opinion in neurology 16, 443-449,
doi:10.1097/01.wco.0000084220.82329.60 (2003).
110 LITERATURVERZEICHNIS
140 Driscoll, M. & Gerstbrein, B. Dying for a cause: invertebrate genetics takes on human neurodegeneration. Nature reviews. Genetics 4, 181-194, doi:10.1038/nrg1018 (2003).
141 Sabbagh, J. J., Kinney, J. W. & Cummings, J. L. Animal systems in the development of treatments for Alzheimer's disease: challenges, methods, and implications.
Neurobiol Aging 34, 169-183, doi:10.1016/j.neurobiolaging.2012.02.027 (2013).
142 Abeliovich, A. et al. Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25, 239-252 (2000).
143 Dauer, W. et al. Resistance of alpha -synuclein null mice to the parkinsonian neurotoxin MPTP. Proc Natl Acad Sci U S A 99, 14524-14529, doi:10.1073/pnas.172514599 (2002).
144 Schluter, O. M. et al. Role of alpha-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice. Neuroscience 118, 985-1002 (2003).
145 Fernagut, P. O. & Chesselet, M. F. Alpha-synuclein and transgenic mouse models.
Neurobiol Dis 17, 123-130, doi:10.1016/j.nbd.2004.07.001 (2004).
146 Yamashita, H. et al. Embryonic stem cell-derived neuron models of Parkinson's disease exhibit delayed neuronal death. J Neurochem 98, 45-56, doi:10.1111/j.1471-4159.2006.03815.x (2006).
147 Crabtree, D. M. & Zhang, J. Genetically engineered mouse models of Parkinson's disease. Brain research bulletin 88, 13-32, doi:10.1016/j.brainresbull.2011.07.019 (2012).
148 Blandini, F. & Armentero, M. T. Animal models of Parkinson's disease. Febs J 279, 1156-1166, doi:10.1111/j.1742-4658.2012.08491.x (2012).
149 Wolozin, B., Gabel, C., Ferree, A., Guillily, M. & Ebata, A. Watching worms whither: modeling neurodegeneration in C. elegans. Prog Mol Biol Transl Sci 100, 499-514, doi:10.1016/B978-0-12-384878-9.00015-7 (2011).
150 Link, C. D. Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans. Proc Natl Acad Sci U S A 92, 9368-9372 (1995).
151 Lakso, M. et al. Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human alpha-synuclein. J Neurochem 86, 165-172 (2003).
152 Hamamichi, S. et al. Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson's disease model. Proc Natl Acad Sci U S A 105, 728-733, doi:10.1073/pnas.0711018105 (2008).
LITERATURVERZEICHNIS 111
153 van Ham, T. J. et al. C. elegans model identifies genetic modifiers of alpha-synuclein inclusion formation during aging. PLoS genetics 4, e1000027, doi:10.1371/journal.pgen.1000027 (2008).
154 Nass, R. & Blakely, R. D. The Caenorhabditis elegans dopaminergic system:
opportunities for insights into dopamine transport and neurodegeneration. Annual
review of pharmacology and toxicology 43, 521-544,
doi:10.1146/annurev.pharmtox.43.100901.135934 (2003).
155 Nass, R., Hall, D. H., Miller, D. M., 3rd & Blakely, R. D. Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans. Proc Natl Acad Sci U S A 99, 3264-3269, doi:10.1073/pnas.042497999 (2002).
156 Wheeler, V. C. et al. Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice. Hum Mol Genet 9, 503-513 (2000).
157 Lee, C. Y., Cantle, J. P. & Yang, X. W. Genetic manipulations of mutant huntingtin in mice: new insights into Huntington's disease pathogenesis. Febs J, doi:10.1111/febs.12418 (2013).
158 Heath, P. R. & Shaw, P. J. Update on the glutamatergic neurotransmitter system and the role of excitotoxicity in amyotrophic lateral sclerosis. Muscle & nerve 26, 438-458, doi:10.1002/mus.10186 (2002).
158 Heath, P. R. & Shaw, P. J. Update on the glutamatergic neurotransmitter system and the role of excitotoxicity in amyotrophic lateral sclerosis. Muscle & nerve 26, 438-458, doi:10.1002/mus.10186 (2002).