Gene expression profiling and therapeutic interventions in neurodegenerative diseases: A comprehensive study on potentiality and limits

Expert Opinion on Drug Discovery

Volumn 7, Issue 3, 2012, Pages 245-259

  Benetti, Federico ^a,b   Gustincich, Stefano ^a   Legname, Giuseppe ^a,b,c  

^a SISSA   (Italy)

^b ISTITUTO ITALIANO DI TECNOLOGIA   (Italy)

^c SINCROTRONE TRIESTE   (Italy)

Author keywords

Alzheimer's disease; Drug; Gene expression; Huntington's disease; Parkinson's disease; Prion diseases

Indexed keywords

3 NITROTYROSINE; 8 HYDROXYDEOXYGUANOSINE; ALPHA SYNUCLEIN; ALPHA TOCOPHEROL; ALZHEIMER DISEASE VACCINE; AMANTADINE; ANTIOXIDANT; APOMORPHINE; BENZOTHIAZOLE DERIVATIVE; BIOLOGICAL MARKER; CARBIDOPA; CHOLINESTERASE INHIBITOR; DIMEBON; ENTACAPONE; FLUPIRTINE; LEUPRORELIN; LEVODOPA; LITHIUM CHLORIDE; MELATONIN; MEMANTINE; METHYLENE BLUE; MULTIDRUG RESISTANCE PROTEIN 1; PENTOSAN POLYSULFATE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; POLYENE ANTIBIOTIC AGENT; REACTIVE OXYGEN METABOLITE; SEROTONIN UPTAKE INHIBITOR; UBIDECARENONE; UNINDEXED DRUG; URIC ACID;

ALZHEIMER DISEASE; DEGENERATIVE DISEASE; DRUG MECHANISM; DRUG TARGETING; DYSKINESIA; FUNCTIONAL PROTEOMICS; GENE EXPRESSION PROFILING; GENETIC TRANSCRIPTION; HALLUCINATION; HUMAN; HUNTINGTON CHOREA; INVOLUNTARY MOVEMENT; MICROARRAY ANALYSIS; MOTOR DYSFUNCTION; NAUSEA; NEUROPATHOLOGY; NONHUMAN; ORTHOSTATIC HYPOTENSION; OXIDATIVE STRESS; PARKINSON DISEASE; PRION DISEASE; PRIORITY JOURNAL; REVIEW; SEDATION; SIDE EFFECT;

ANIMALS; BIOLOGICAL MARKERS; DRUG DELIVERY SYSTEMS; DRUG DESIGN; DRUG DISCOVERY; GENE EXPRESSION PROFILING; HUMANS; NEURODEGENERATIVE DISEASES; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PROTEOMICS;

EID: 84857554581     PISSN: 17460441     EISSN: 1746045X     Source Type: Journal    
DOI: 10.1517/17460441.2012.659661     Document Type: Review

References (144)

1. Galimberti D, Scarpini E. Progress in Alzheimer's disease. J Neurol 2012;259(2):201-11
2. Heisters D. Parkinson's: symptoms, treatments and research. Br J Nurs 2011;20(9):548-54
3. Shoulson I, Young AB. Milestones in huntington disease. Mov Disord 2011;26(6):1127-33
4. Benetti F, Legname G. De novo mammalian prion synthesis. Prion 2009;3(4):213-19
5. Yang Y, Adelstein SJ, Kassis AI. Target discovery from data mining approaches. Drug Discov Today 2009;14(3-4):147-54
6. di Bernardo D, Thompson MJ, Gardner TS, et al. Chemogenomic profiling on a genome-wide scale using reverse-engineered gene networks. Nat Biotechnol 2005;23(3):377-83 (Pubitemid 41094431)
7. Gardner TS, di Bernardo D, Lorenz D, et al. Inferring genetic networks and identifying compound mode of action via expression profiling. Science 2003;301(5629):102-5 (Pubitemid 36801571)
8. Stone JG, Casadesus G, Gustaw-Rothenberg K, et al. Frontiers in Alzheimer's Disease Therapeutics. Ther Adv Chronic Dis 2011;2(1):9-23
9. Zhang YW, Thompson R, Zhang H, et al. APP processing in Alzheimer's disease. Mol Brain 2011;4:3
10. Bertram L, McQueen MB, Mullin K, et al. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet 2007;39(1):17-23 (Pubitemid 46026496)
11. Ho L, Guo Y, Spielman L, et al. Altered expression of a-type but not b-type synapsin isoform in the brain of patients at high risk for Alzheimer's disease assessed by DNA microarray technique. Neurosci Lett 2001;298(3):191-4 (Pubitemid 32126384)
12. Ho L, Sharma N, Blackman L, et al. From proteomics to biomarker discovery in Alzheimer's disease. Brain Res Brain Res Rev 2005;48(2):360-9 (Pubitemid 40585767)
13. Yao PJ, Zhu M, Pyun EI, et al. Defects in expression of genes related to synaptic vesicle trafficking in frontal cortex of Alzheimer's disease. Neurobiol Dis 2003;12(2):97-109 (Pubitemid 36355860)
14. Loring JF, Wen X, Lee JM, et al. A gene expression profile of Alzheimer's disease. DNA Cell Biol 2001;20(11):683-95 (Pubitemid 34072835)
15. Colangelo V, Schurr J, Ball MJ, et al. Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling. J Neurosci Res 2002;70(3):462-73 (Pubitemid 35222383)
16. Murphy MP. Development of lipophilic cations as therapies for disorders due to mitochondrial dysfunction. Expert Opin Biol Ther 2001;1(5):753-64 (Pubitemid 33769735)
17. t' Veld BA, Ruitenberg A, Hofman A, et al. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. N Engl J Med 2001;345(21):1515-21 (Pubitemid 33144916)
18. Cornelius C, Fastbom J, Winblad B, et al. Aspirin, NSAIDs, risk of dementia, and influence of the apolipoprotein E epsilon 4 allele in an elderly population. Neuroepidemiology 2004;23(3):135-43 (Pubitemid 38490224)
19. Lindsay J, Laurin D, Verreault R, et al. Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol 2002;156(5):445-53 (Pubitemid 34976983)
20. Liu G, Men P, Kudo W, et al. Nanoparticle-chelator conjugates as inhibitors of amyloid-beta aggregation and neurotoxicity: a novel therapeutic approach for Alzheimer disease. Neurosci Lett 2009;455(3):187-90
21. Liang WS, Dunckley T, Beach TG, et al. Altered neuronal gene expression in brain regions differentially affected by Alzheimer's disease: a reference data set. Physiol Genomics 2008;33(2):240-56 (Pubitemid 351629532)
22. Sullivan PF, Fan C, Perou CM. Evaluating the comparability of gene expression in blood and brain. Am J Med Genet B Neuropsychiatr Genet 2006;141B(3):261-8
23. Booij BB, Lindahl T, Wetterberg P, et al. A gene expression pattern in blood for the early detection of Alzheimer's disease. J Alzheimers Dis 2011;23(1):109-19
24. Nguyen DV, Rocke DM. Tumor classification by partial least squares using microarray gene expression data. Bioinformatics 2002;18(1):39-50 (Pubitemid 34145030)
25. Gidskehaug L, Anderssen E, Flatberg A, et al. A framework for significance analysis of gene expression data using dimension reduction methods. BMC Bioinformatics 2007;8:346
26. Scherzer CR, Offe K, Gearing M, et al. Loss of apolipoprotein E receptor LR11 in Alzheimer disease. Arch Neurol 2004;61(8):1200-5 (Pubitemid 39062672)
27. Dodson SE, Gearing M, Lippa CF, et al. LR11/SorLA expression is reduced in sporadic Alzheimer disease but not in familial Alzheimer disease. J Neuropathol Exp Neurol 2006;65(9):866-72 (Pubitemid 44371232)
28. Sager KL, Wuu J, Leurgans SE, et al. Neuronal LR11/sorLA expression is reduced in mild cognitive impairment. Ann Neurol 2007;62(6):640-7
29. Rogaeva E, Meng Y, Lee JH, et al. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet 2007;39(2):168-77 (Pubitemid 46184347)
30. Reitz C, Cheng R, Rogaeva E, et al. Meta-analysis of the association between variants in SORL1 and Alzheimer disease. Arch Neurol 2011;68(1):99-106
31. Chen KD, Chang PT, Ping YH, et al. Gene expression profiling of peripheral blood leukocytes identifies and validates ABCB1 as a novel biomarker for Alzheimer's disease. Neurobiol Dis 2011;43(3):698-705
32. Forero DA. Genome-wide expression profiles in Alzheimer's and Parkinson's diseases. In preparation (http://sites.google.com/site/compgensite/ad-pd- arraylist)
33. Brookmeyer R, Johnson E, Ziegler-Graham K, et al. Forecasting the global burden of Alzheimer's disease. Alzheimers Dement 2007;3(3):186-91 (Pubitemid 46825511)
34. Corrada MM, Kawas CH, Hallfrisch J, et al. Reduced risk of Alzheimer's disease with high folate intake: the Baltimore Longitudinal Study of Aging. Alzheimers Dement 2005;1(1):11-18 (Pubitemid 43348849)
35. Zandi PP, Anthony JC, Khachaturian AS, et al. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol 2004;61(1):82-8 (Pubitemid 38067418)
36. Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's disease cooperative study. N Engl J Med 1997;336(17):1216-22 (Pubitemid 27183651)
37. Aisen PS, Davis KL, Berg JD, et al. A randomized controlled trial of prednisone in Alzheimer's disease. Alzheimer's disease cooperative study. Neurology 2000;54(3):588-93 (Pubitemid 30082922)
38. Aisen PS, Schafer KA, Grundman M, et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 2003;289(21):2819-26 (Pubitemid 37430117)
39. Van Gool WA, Weinstein HC, Scheltens P, et al. Effect of hydroxychloroquine on progression of dementia in early Alzheimer's disease: an 18-month randomised, double-blind, placebo-controlled study. Lancet 2001;358(9280):455-60 (Pubitemid 32769852)
40. Reines SA, Block GA, Morris JC, et al. Rofecoxib: no effect on Alzheimer's disease in a 1-year, randomized, blinded, controlled study. Neurology 2004;62(1):66-71 (Pubitemid 38082872)
41. Strozyk D, Bush AI. The role of metal ions in neurology. An introduction. Met Ions Life Sci 2006;1:1-7
42. Parks JK, Smith TS, Trimmer PA, et al. Neurotoxic abeta peptides increase oxidative stress in vivo through NMDA-receptor and nitric-oxidesynthase mechanisms, and inhibit complex IV activity and induce a mitochondrial permeability transition in vitro. J Neurochem 2001;76(4):1050-6 (Pubitemid 32167378)
43. Doody RS, Gavrilova SI, Sano M, et al. Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study. Lancet 2008;372(9634):207-15 (Pubitemid 351978110)
44. Bowen RL, Isley JP, Atkinson RL: An association of elevated serum gonadotropin concentrations and Alzheimer disease? J Neuroendocrinol 2000;12(4):351-4 (Pubitemid 30156528)
45. Short RA, Bowen RL, O'Brien PC, et al. Elevated gonadotropin levels in patients with Alzheimer disease. Mayo Clin Proc 2001;76(9):906-9 (Pubitemid 32825912)
46. Webber KM, Casadesus G, Bowen RL, et al. Evidence for the role of luteinizing hormone in Alzheimer disease. Endocr Metab Immune Disord Drug Targets 2007;7(4):300-3
47. Noble W, Planel E, Zehr C, et al. Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo. Proc Natl Acad Sci USA 2005;102(19):6990-5 (Pubitemid 40675429)
48. Neugroschl J, Sano M. An update on treatment and prevention strategies for Alzheimer's disease. Curr Neurol Neurosci Rep 2009;9(5):368-76
49. Luo W, Dou F, Rodina A, et al. Roles of heat-shock protein 90 in maintaining and facilitating the neurodegenerative phenotype in tauopathies. Proc Natl Acad Sci USA 2007;104(22):9511-16 (Pubitemid 47185810)
50. Himeno E, Ohyagi Y, Ma L, et al. Apomorphine treatment in Alzheimer mice promoting amyloid-beta degradation. Ann Neurol 2011;69(2):248-56
51. Olcese JM, Cao C, Mori T, et al. Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease. J Pineal Res 2009;47(1):82-96
52. Shah S, Federoff HJ. Therapeutic potential of vaccines for Alzheimer's disease. Immunotherapy 2011;3(2):287-98
53. Menendez-Gonzalez M, Perez-Pinera P, Martinez-Rivera M, et al. Immunotherapy for Alzheimer's disease: rational basis in ongoing clinical trials. Curr Pharm Des 2011;17(5):508-20
54. Handley OJ, Naji JJ, Dunnett SB, et al. Pharmaceutical, cellular and genetic therapies for Huntington's disease. Clin Sci (Lond) 2006;110(1):73-88 (Pubitemid 43059046)
55. Vonsattel JP, Myers RH, Stevens TJ, et al. Neuropathological classification of Huntington's disease. J Neuropathol Exp Neurol 1985;44(6):559-77 (Pubitemid 16196286)
56. Hedreen JC, Peyser CE, Folstein SE, et al. Neuronal loss in layers V and VI of cerebral cortex in Huntington's disease. Neurosci Lett 1991;133(2):257-61
57. Jarabek BR, Yasuda RP, Wolfe BB. Regulation of proteins affecting NMDA receptor-induced excitotoxicity in a Huntington's mouse model. Brain 2004;127(Pt 3):505-16 (Pubitemid 38295468)
58. Li JY, Plomann M, Brundin P: Huntington's disease: a synaptopathy? Trends Mol Med 2003;9(10):414-20 (Pubitemid 37309642)
59. Beal MF, Ferrante RJ. Experimental therapeutics in transgenic mouse models of Huntington's disease. Nat Rev Neurosci 2004;5(5):373-84 (Pubitemid 38568498)
60. Kumar P, Kalonia H, Kumar A. Huntington's disease: pathogenesis to animal models. Pharmacol Rep 2010;62(1):1-14
61. Cha JH. Transcriptional signatures in Huntington's disease. Prog Neurobiol 2007;83(4):228-48
62. Hodges A, Strand AD, Aragaki AK, et al. Regional and cellular gene expression changes in human Huntington's disease brain. Hum Mol Genet 2006;15(6):965-77 (Pubitemid 43338237)
63. Hannan AJ. Novel therapeutic targets for Huntington's disease. Expert Opin Ther Targets 2005;9(4):639-50 (Pubitemid 41131671)
64. Krobitsch S, Kazantsev AG. Huntington's disease: from molecular basis to therapeutic advances. Int J Biochem Cell Biol 2011;43(1):20-4
65. Hersch SM, Rosas HD. Neuroprotection for Huntington's disease: ready, set, slow. Neurotherapeutics 2008;5(2):226-36 (Pubitemid 351446208)
66. Yamamoto A, Lucas JJ, Hen R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 2000;101(1):57-66
67. Diaz-Hernandez M, Torres-Peraza J, Salvatori-Abarca A, et al. Full motor recovery despite striatal neuron loss and formation of irreversible amyloid-like inclusions in a conditional mouse model of Huntington's disease. J Neurosci 2005;25(42):9773-81 (Pubitemid 41510917)
68. Heiser V, Engemann S, Brocker W, et al. Identification of benzothiazoles as potential polyglutamine aggregation inhibitors of Huntington's disease by using an automated filter retardation assay. Proc Natl Acad Sci USA 2002;99(Suppl 4):16400-6 (Pubitemid 35470985)
69. Morgan JC, Mehta SH, Sethi KD. Biomarkers in Parkinson's disease. Curr Neurol Neurosci Rep 2010;10(6):423-30
70. de Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet Neurol 2006;5(6):525-35 (Pubitemid 44262284)
71. Greggio E, Bisaglia M, Civiero L, et al: Leucine-rich repeat kinase 2 and alphasynuclein: intersecting pathways in the pathogenesis of Parkinson's disease? Mol Neurodegener 2011;6(1):6
72. Warner TT, Schapira AH. Genetic and environmental factors in the cause of Parkinson's disease. Ann Neurol 2003;53(Suppl 3):S16-23; discussion S-5
73. Gibb WR, Lees AJ. The significance of the Lewy body in the diagnosis of idiopathic Parkinson's disease. Neuropathol Appl Neurobiol 1989;15(1):27-44 (Pubitemid 19074096)
74. Sundal C, Fujioka S, Uitti RJ, et al. Autosomal dominant Parkinson's disease. Parkinsonism Relat Disord 2012;18(Suppl 1):S7-10
75. Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 1997;276(5321):2045-7 (Pubitemid 27443610)
76. Kitada T, Asakawa S, Hattori N, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 1998;392(6676):605-8 (Pubitemid 28207717)
77. Bonifati V, Rizzu P, van Baren MJ, et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 2003;299(5604):256-9 (Pubitemid 36131051)
78. Valente EM, Abou-Sleiman PM, Caputo V, et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 2004;304(5674):1158-60 (Pubitemid 38661852)
79. Singleton AB, Farrer M, Johnson J, et al. alpha-Synuclein locus triplication causes Parkinson's disease. Science 2003;302(5646):841 (Pubitemid 37339619)
80. Leroy E, Boyer R, Auburger G, et al. The ubiquitin pathway in Parkinson's disease. Nature 1998;395(6701):451-2
81. Nalls MA, Plagnol V, Hernandez DG, et al. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet 2011;377(9766):641-9
82. El-Agnaf OM, Salem SA, Paleologou KE, et al. Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease. FASEB J 2006;20(3):419-25 (Pubitemid 44933318)
83. Mollenhauer B, Cullen V, Kahn I, et al. Direct quantification of CSF alpha-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration. Exp Neurol 2008;213(2):315-25
84. Hoepken HH, Gispert S, Azizov M, et al. Parkinson patient fibroblasts show increased alpha-synuclein expression. Exp Neurol 2008;212(2):307-13
85. Ihara Y, Chuda M, Kuroda S, et al. Hydroxyl radical and superoxide dismutase in blood of patients with Parkinson's disease: relationship to clinical data. J Neurol Sci 1999;170(2):90-5 (Pubitemid 29528530)
86. Sato S, Mizuno Y, Hattori N. Urinary 8-hydroxydeoxyguanosine levels as a biomarker for progression of Parkinson disease. Neurology 2005;64(6):1081-3 (Pubitemid 40388471)
87. Schwarzschild MA, Schwid SR, Marek K, et al. Serum urate as a predictor of clinical and radiographic progression in Parkinson disease. Arch Neurol 2008;65(6):716-23 (Pubitemid 351831449)
88. Schlesinger I, Schlesinger N. Uric acid in Parkinson's disease. Mov Disord 2008;23(12):1653-7
89. Ascherio A, LeWitt PA, Xu K, et al. Urate as a predictor of the rate of clinical decline in Parkinson disease. Arch Neurol 2009;66(12):1460-8
90. Hauser MA, Li YJ, Xu H, et al. Expression profiling of substantia nigra in Parkinson disease, progressive supranuclear palsy, and frontotemporal dementia with parkinsonism. Arch Neurol 2005;62(6):917-21 (Pubitemid 40973453)
91. Mandel S, Grunblatt E, Riederer P, et al. Gene expression profiling of sporadic Parkinson's disease substantia nigra pars compacta reveals impairment of ubiquitin-proteasome subunits, SKP1A, aldehyde dehydrogenase, and chaperone HSC-70. Ann N Y Acad Sci 2005;1053:356-75 (Pubitemid 43031116)
92. Duke DC, Moran LB, Kalaitzakis ME, et al. Transcriptome analysis reveals link between proteasomal and mitochondrial pathways in Parkinson's disease. Neurogenetics 2006;7(3):139-48 (Pubitemid 44078291)
93. Moran LB, Duke DC, Deprez M, et al. Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's disease. Neurogenetics 2006;7(1):1-11 (Pubitemid 43327678)
94. Hastie T, Tibshirani R, Eisen MB, et al. 'Gene shaving' as a method for identifying distinct sets of genes with similar expression patterns. Genome Biol 2000;1(2):RESEARCH0003
95. McRitchie DA, Hardman CD, Halliday GM. Cytoarchitectural distribution of calcium binding proteins in midbrain dopaminergic regions of rats and humans. J Comp Neurol 1996;364(1):121-50 (Pubitemid 26026640)
96. Grimm J, Mueller A, Hefti F, et al. Molecular basis for catecholaminergic neuron diversity. Proc Natl Acad Sci USA 2004;101(38):13891-6 (Pubitemid 39298503)
97. Greene JG, Dingledine R, Greenamyre JT. Gene expression profiling of rat midbrain dopamine neurons: implications for selective vulnerability in parkinsonism. Neurobiol Dis 2005;18(1):19-31 (Pubitemid 40092894)
98. Matus A. MARCKS for maintenance in dendritic spines. Neuron 2005;48(1):4-5 (Pubitemid 41384158)
99. Paradis E, Clement S, Julien P, et al. Lipoprotein lipase affects the survival and differentiation of neural cells exposed to very low density lipoprotein. J Biol Chem 2003;278(11):9698-705 (Pubitemid 36805605)
100. Chung CY, Seo H, Sonntag KC, et al. Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protection. Hum Mol Genet 2005;14(13):1709-25 (Pubitemid 41418045)
101. Inaba S, Li C, Shi YE, et al. Synuclein gamma inhibits the mitotic checkpoint function and promotes chromosomal instability of breast cancer cells. Breast Cancer Res Treat 2005;94(1):25-35 (Pubitemid 41416939)
102. Kress GJ, Reynolds IJ. Dopaminergic neurotoxins require excitotoxic stimulation in organotypic cultures. Neurobiol Dis 2005;20(3):639-45 (Pubitemid 41619340)
103. Greenamyre JT, Sherer TB, Betarbet R, et al. Complex I and Parkinson's disease. IUBMB Life 2001;52(3-5):135-41 (Pubitemid 33731566)
104. Betarbet R, Sherer TB, MacKenzie G, et al. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 2000;3(12):1301-6
105. Palacino JJ, Sagi D, Goldberg MS, et al. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem 2004;279(18):18614-22 (Pubitemid 38623283)
106. Biagioli M, Pinto M, Cesselli D, et al. Unexpected expression of alpha- and beta-globin in mesencephalic dopaminergic neurons and glial cells. Proc Natl Acad Sci USA 2009;106(36):15454-9
107. Scherzer CR, Eklund AC, Morse LJ, et al. Molecular markers of early Parkinson's disease based on gene expression in blood. Proc Natl Acad Sci USA 2007;104(3):955-60 (Pubitemid 46154718)
108. Mutez E, Larvor L, Lepretre F, et al. Transcriptional profile of Parkinson blood mononuclear cells with LRRK2 mutation. Neurobiol Aging 2010;32(10):1839-48
109. Zheng B, Liao Z, Locascio JJ, et al. PGC-1alpha, a potential therapeutic target for early intervention in Parkinson's disease. Sci Transl Med 2010;2(52):52-73
110. Taccioli C, Tegner J, Maselli V, et al. ParkDB: a Parkinson's disease gene expression database. Database (Oxford) 2011;2011:bar007
111. Rezak M. Current pharmacotherapeutic treatment options in Parkinson's disease. Dis Mon 2007;53(4):214-22 (Pubitemid 46935688)
112. Cotzias GC, Van Woert MH, Schiffer LM. Aromatic amino acids and modification of parkinsonism. N Engl J Med 1967;276(7):374-9
113. Chen JJ, Wilkinson JR. The Monoamine Oxidase Type B Inhibitor Rasagiline in the Treatment of Parkinson Disease: Is Tyramine a Challenge? J Clin Pharmacol 2011. [Epub ahead of print]
114. Weinreb O, Amit T, Bar-Am O, et al. Rasagiline: a novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity. Prog Neurobiol 2010;92(3):330-44
115. Prusiner SB. Prions. Proc Natl Acad Sci USA 1998;95(23):13363-83 (Pubitemid 28525623)
116. Mead S, Stumpf MP, Whitfield J, et al. Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics. Science 2003;300(5619):640-3 (Pubitemid 36520588)
117. Collinge J, Clarke AR. A general model of prion strains and their pathogenicity. Science 2007;318(5852):930-6 (Pubitemid 350098981)
118. Legname G, Nguyen HO, Peretz D, et al. Continuum of prion protein structures enciphers a multitude of prion isolate-specified phenotypes. Proc Natl Acad Sci USA 2006;103(50):19105-10 (Pubitemid 350002835)
119. Aguzzi A, Sigurdson C, Heikenwaelder M. Molecular mechanisms of prion pathogenesis. Annu Rev Pathol 2008;3:11-40 (Pubitemid 351488275)
120. van der Kamp MW, Daggett V. The consequences of pathogenic mutations to the human prion protein. Protein Eng Des Sel 2009;22(8):461-8
121. Benetti F, Gasperini L, Zampieri M, et al. Gene expression profiling to identify druggable targets in prion diseases. Expert Opin Drug Discov 2010;5(2):177-202
122. Xiang W, Windl O, Westner IM, et al. Cerebral gene expression profiles in sporadic Creutzfeldt-Jakob disease. Ann Neurol 2005;58(2):242-57 (Pubitemid 41098882)
123. Trevitt CR, Collinge J. A systematic review of prion therapeutics in experimental models. Brain 2006;129(Pt 9):2241-65 (Pubitemid 44522112)
124. Masullo C, Macchi G, Xi YG, et al. Failure to ameliorate Creutzfeldt-Jakob disease with amphotericin B therapy. J Infect Dis 1992;165(4):784-5
125. Stewart LA, Rydzewska LH, Keogh GF, et al. Systematic review of therapeutic interventions in human prion disease. Neurology 2008;70(15):1272-81 (Pubitemid 351520951)
126. Pocchiari M, Casaccia P, Ladogana A. Amphotericin B: a novel class of antiscrapie drugs. J Infect Dis 1989;160(5):795-802 (Pubitemid 19266835)
127. Brajtburg J, Elberg S, Bolard J, et al. Interaction of plasma proteins and lipoproteins with amphotericin B. J Infect Dis 1984;149(6):986-97 (Pubitemid 14082164)
128. Taraboulos A, Scott M, Semenov A, et al. Cholesterol depletion and modification of COOH-terminal targeting sequence of the prion protein inhibit formation of the scrapie isoform. J Cell Biol 1995;129(1):121-32
129. Bate C, Salmona M, Diomede L, et al. Squalestatin cures prion-infected neurons and protects against prion neurotoxicity. J Biol Chem 2004;279(15):14983-90 (Pubitemid 38618891)
130. Mok SW, Thelen KM, Riemer C, et al. Simvastatin prolongs survival times in prion infections of the central nervous system. Biochem Biophys Res Commun 2006;348(2):697-702 (Pubitemid 44188620)
131. Kempster S, Bate C, Williams A. Simvastatin treatment prolongs the survival of scrapie-infected mice. Neuroreport 2007;18(5):479-82 (Pubitemid 46668038)
132. Engelstein R, Grigoriadis N, Greig NH, et al. Inhibition of P53-related apoptosis had no effect on PrP(Sc) accumulation and prion disease incubation time. Neurobiol Dis 2005;18(2):282-5 (Pubitemid 40431111)
133. Perovic S, Schroder HC, Pergande G, et al. Effect of flupirtine on Bcl-2 and glutathione level in neuronal cells treated in vitro with the prion protein fragment (PrP106-126). Exp Neurol 1997;147(2):518-24 (Pubitemid 27497313)
134. Sigurdsson EM, Brown DR, Alim MA, et al. Copper chelation delays the onset of prion disease. J Biol Chem 2003;278(47):46199-202 (Pubitemid 37452189)
135. Drisko JA. The use of antioxidants in transmissible spongiform encephalopathies: a case report. J Am Coll Nutr 2002;21(1):22-5 (Pubitemid 34123705)
136. Chevyreva I, Faull RL, Green CR, et al. Assessing RNA quality in postmortem human brain tissue. Exp Mol Pathol 2008;84(1):71-7 (Pubitemid 351163260)
137. Lipska BK, Deep-Soboslay A, Weickert CS, et al. Critical factors in gene expression in postmortem human brain: focus on studies in schizophrenia. Biol Psychiatry 2006;60(6):650-8 (Pubitemid 44402385)
138. Sutherland GT, Janitz M, Kril JJ: Understanding the pathogenesis of Alzheimer's disease: will RNA-Seq realize the promise of transcriptomics? J Neurochem 2011;116(6):937-46
139. Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet 2009;10(1):57-63
140. Martin JA, Wang Z. Next-generation transcriptome assembly. Nat Rev Genet 2011;12(10):671-82
141. Twine NA, Janitz K, Wilkins MR, et al. Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease. PLoS ONE 2011;6(1):e16266
142. Leskovjan AC, Lanzirotti A, Miller LM. Amyloid plaques in PSAPP mice bind less metal than plaques in human Alzheimer's disease. Neuroimage 2009;47(4):1215-20
143. Pushie MJ, Pickering IJ, Martin GR, et al. Prion protein expression level alters regional copper, iron and zinc content in the mouse brain. Metallomics 2011;3(2):206-14
144. Domazet B, Maclennan GT, Lopez-Beltran A, et al. Laser capture microdissection in the genomic and proteomic era: targeting the genetic basis of cancer. Int J Clin Exp Pathol 2008;1(6):475-88