Molecular pathways and genetic aspects of Parkinson’s disease: from bench to bedside

References

• Twelves D, Perkins KS, Counsell C. Systematic review of incidence studies of Parkinson’s disease. Mov. Disord.18(1), 19–31 (2003).
   PubMed Web of Science ®Google Scholar
• Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sorensen P. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch. Neurol.60(3), 387–392 (2003).
   PubMed Web of Science ®Google Scholar
• Hughes AJ, Daniel SE, Lees AJ. Improved accuracy of clinical diagnosis of Lewy body Parkinson’s disease. Neurology57(8), 1497–1499 (2001).
   PubMed Web of Science ®Google Scholar
• Dorsey ER, Holloway RG, Ravina BM. Biomarkers in Parkinson’s disease. Expert Rev. Neurother.6(6), 823–831 (2006).
   PubMedGoogle Scholar
• van Laere K, Casteels C, de Ceuninck L et al. Dual-tracer dopamine transporter and perfusion SPECT in differential diagnosis of parkinsonism using template-based discriminant analysis. J. Nucl. Med.47(3), 384–392 (2006).
   PubMed Web of Science ®Google Scholar
• Berg D, Hochstrasser H, Schweitzer KJ, Riess O. Disturbance of iron metabolism in Parkinson’s disease-ultrasonography as a biomarker. Neurotox. Res.9(1), 1–13 (2006).
   PubMed Web of Science ®Google Scholar
• Ponsen MM, Stoffers D, Booij J, Eck-Smit BL, Wolters EC, Berendse HW. Idiopathic hyposmia as a preclinical sign of Parkinson’s disease. Ann. Neurol.56(2), 173–181 (2004).
   PubMed Web of Science ®Google Scholar
• El Agnaf OM, Salem SA, Paleologou KE et al. Detection of oligomeric forms of α-synuclein protein in human plasma as a potential biomarker for Parkinson’s disease. FASEB J.20(3), 419–425 (2006).
   PubMedGoogle Scholar
• Guilloteau D, Chalon S. PET and SPECT exploration of central monoaminergic transporters for the development of new drugs and treatments in brain disorders. Curr. Pharm. Des.11(25), 3237–3245 (2005).
   PubMed Web of Science ®Google Scholar
• Michell AW, Lewis SJ, Foltynie T, Barker RA. Biomarkers and Parkinson’s disease. Brain127(8), 1693–1705 (2004).
   PubMed Web of Science ®Google Scholar
• Braak H, Bohl JR, Muller CM, Rub U, de Vos RA, Del Tredici K. Stanley Fahn Lecture 2005: the staging procedure for the inclusion body pathology associated with sporadic Parkinson’s disease reconsidered. Mov. Disord.21(12), 2042–2051 (2006).
   PubMed Web of Science ®Google Scholar
• Wolters EC, Braak H. Parkinson’s disease: premotor clinico-pathological correlations. J. Neural Transm.70(Suppl.), 309–319 (2006).
   Google Scholar
• Poewe WH, Wenning GK. The natural history of Parkinson’s disease. Ann. Neurol.44(3 Suppl. 1), S1–S9 (1998).
   Google Scholar
• Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science219(4587), 979–980 (1983).
   PubMed Web of Science ®Google Scholar
• Jeon BS, Jackson-Lewis V, Burke RE. 6-hydroxydopamine lesion of the rat substantia nigra: time course and morphology of cell death. Neurodegeneration4(2), 131–137 (1995).
   PubMedGoogle Scholar
• Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat. Neurosci.3(12), 1301–1306 (2000).
   PubMed Web of Science ®Google Scholar
• Benamer HT, Patterson J, Wyper DJ, Hadley DM, Macphee GJ, Grosset DG. Correlation of Parkinson’s disease severity and duration with 123I-FP-CIT SPECT striatal uptake. Mov. Disord.15(4), 692–698 (2000).
   PubMed Web of Science ®Google Scholar
• Braak H, Ghebremedhin E, Rub U, Bratzke H, del Tredici K. Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res.318(1), 121–134 (2004).
   PubMed Web of Science ®Google Scholar
• Iranzo A, Molinuevo JL, Santamaria J et al. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol.5(7), 572–577 (2006).
   PubMed Web of Science ®Google Scholar
• Boeve BF, Silber MH, Saper CB et al. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. BrainDOI:10.1093/brain/awm056 (Epub ahead of print) (2007).
   Google Scholar
• Stiasny-Kolster K, Doerr Y, Moller JC et al. Combination of ‘idiopathic’ REM sleep behaviour disorder and olfactory dysfunction as possible indicator for α-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain128(1), 126–137 (2005).
   PubMed Web of Science ®Google Scholar
• McNaught KS, Olanow CW, Halliwell B, Isacson O, Jenner P. Failure of the ubiquitin-proteasome system in Parkinson’s disease. Nat. Rev. Neurosci.2(8), 589–594 (2001).
   PubMed Web of Science ®Google Scholar
• McNaught KS, Jackson T, JnoBaptiste R, Kapustin A, Olanow CW. Proteasomal dysfunction in sporadic Parkinson’s disease. Neurology66(10 Suppl. 4), S37–S49 (2006).
   PubMedGoogle Scholar
• Wolf DH, Hilt W. The proteasome: a proteolytic nanomachine of cell regulation and waste disposal. Biochim. Biophys. Acta1695(1–3), 19–31 (2004).
   PubMed Web of Science ®Google Scholar
• Adams J. The proteasome: structure, function, and role in the cell. Cancer Treat. Rev.29(Suppl. 1), 3–9 (2003).
   PubMed Web of Science ®Google Scholar
• Pines J, Lindon C. Proteolysis: anytime, any place, anywhere? Nat. Cell Biol.7(8), 731–735 (2005).
   PubMedGoogle Scholar
• Sherman MY, Goldberg AL. Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases. Neuron29(1), 15–32 (2001).
   PubMed Web of Science ®Google Scholar
• Sawada H, Kohno R, Kihara T et al. Proteasome mediates dopaminergic neuronal degeneration, and its inhibition causes α-synuclein inclusions. J. Biol. Chem.279(11), 10710–10719 (2004).
   PubMed Web of Science ®Google Scholar
• Schapira AH, Cleeter MW, Muddle JR, Workman JM, Cooper JM, King RH. Proteasomal inhibition causes loss of nigral tyrosine hydroxylase neurons. Ann. Neurol.60(2), 253–255 (2006).
   PubMedGoogle Scholar
• McNaught KS, Bjorklund LM, Belizaire R, Isacson O, Jenner P, Olanow CW. Proteasome inhibition causes nigral degeneration with inclusion bodies in rats. Neuroreport13(11), 1437–1441 (2002).
   PubMedGoogle Scholar
• Fornai F, Lenzi P, Gesi M et al. Fine structure and biochemical mechanisms underlying nigrostriatal inclusions and cell death after proteasome inhibition. J. Neurosci.23(26), 8955–8966 (2003).
   PubMed Web of Science ®Google Scholar
• McNaught KS, Perl DP, Brownell AL, Olanow CW. Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson’s disease. Ann. Neurol.56(1), 149–162 (2004).
   PubMed Web of Science ®Google Scholar
• Miwa H, Kubo T, Suzuki A, Nishi K, Kondo T. Retrograde dopaminergic neuron degeneration following intrastriatal proteasome inhibition. Neurosci. Lett.380(1–2), 93–98 (2005).
   PubMedGoogle Scholar
• Zhang X, Xie W, Qu S, Pan T, Wang X, Le W. Neuroprotection by iron chelator against proteasome inhibitor-induced nigral degeneration. Biochem. Biophys. Res. Commun.333(2), 544–549 (2005).
   PubMedGoogle Scholar
• Bove J, Zhou C, Jackson-Lewis V et al. Proteasome inhibition and Parkinson’s disease modeling. Ann. Neurol.60(2), 260–264 (2006).
   PubMed Web of Science ®Google Scholar
• Kordower JH, Kanaan NM, Chu Y et al. Failure of proteasome inhibitor administration to provide a model of Parkinson’s disease in rats and monkeys. Ann. Neurol.60(2), 264–268 (2006).
   PubMed Web of Science ®Google Scholar
• Manning-Bog AB, Reaney SH, Chou VP et al. Lack of nigrostriatal pathology in a rat model of proteasome inhibition. Ann. Neurol.60(2), 256–260 (2006).
   PubMed Web of Science ®Google Scholar
• Langston JW. Parkinson’s disease: current and future challenges. Neurotoxicology23(4–5), 443–450 (2002).
   PubMedGoogle Scholar
• Tanner CM, Ottman R, Goldman SM. Parkinson disease in twins: an etiologic study. JAMA281(4), 341–346 (1999).
   PubMed Web of Science ®Google Scholar
• Fuente-Fernandez R. A note of caution on correlation between sibling pairs. Neurology60(9), 1561 (2003).
   PubMedGoogle Scholar
• Lin MT, Simon DK. No evidence for heritability of Parkinson disease in Swedish twins. Neurology64(5), 932 (2005).
   PubMedGoogle Scholar
• Maher NE, Golbe LI, Lazzarini AM et al. Epidemiologic study of 203 sibling pairs with Parkinson’s disease: the GenePD study. Neurology58(1), 79–84 (2002).
   PubMedGoogle Scholar
• Sveinbjornsdottir S, Hicks AA, Jonsson T et al. Familial aggregation of Parkinson’s disease in Iceland. N. Engl. J. Med.343(24), 1765–1770 (2000).
   PubMed Web of Science ®Google Scholar
• Wirdefeldt K, Gatz M, Schalling M, Pedersen NL. No evidence for heritability of Parkinson disease in Swedish twins. Neurology63(2), 305–311 (2004).
   PubMed Web of Science ®Google Scholar
• Chade AR, Kasten M, Tanner CM. Nongenetic causes of Parkinson’s disease. J. Neural Transm.70(Suppl.), 147–151 (2006).
   Google Scholar
• Brown RC, Lockwood AH, Sonawane BR. Neurodegenerative diseases: an overview of environmental risk factors. Environ. Health Perspect.113(9), 1250–1256 (2005).
   PubMed Web of Science ®Google Scholar
• Logroscino G. The role of early life environmental risk factors in Parkinson disease: what is the evidence? Environ. Health Perspect.113(9), 1234–1238 (2005).
   PubMed Web of Science ®Google Scholar
• Roth JA. Homeostatic and toxic mechanisms regulating manganese uptake, retention, and elimination. Biol. Res.39(1), 45–57 (2006).
   PubMed Web of Science ®Google Scholar
• Coon S, Stark A, Peterson E et al. Whole-body lifetime occupational lead exposure and risk of Parkinson’s disease. Environ. Health Perspect.114(12), 1872–1876 (2006).
   PubMed Web of Science ®Google Scholar
• Thiruchelvam M, Richfield EK, Baggs RB, Tank AW, Cory-Slechta DA. The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: implications for Parkinson’s disease. J. Neurosci.20(24), 9207–9214 (2000).
   PubMed Web of Science ®Google Scholar
• Williams DR. Tauopathies: classification and clinical update on neurodegenerative diseases associated with microtubule-associated protein tau. Intern. Med. J.36(10), 652–660 (2006).
   PubMed Web of Science ®Google Scholar
• Moore DJ, West AB, Dawson VL, Dawson TM. Molecular pathophysiology of Parkinson’s disease. Annu. Rev. Neurosci.28, 57–87 (2005).
   PubMed Web of Science ®Google Scholar
• Hardy J, Cai H, Cookson MR, Gwinn-Hardy K, Singleton A. Genetics of Parkinson’s disease and parkinsonism. Ann. Neurol.60(4), 389–398 (2006).
   PubMed Web of Science ®Google Scholar
• Ramirez A, Heimbach A, Grundemann J et al. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet.38(10), 1184–1191 (2006).
   PubMed Web of Science ®Google Scholar
• Hardy J, Langston JW. How many pathways are there to nigral death? Ann. Neurol.56(3), 316–318 (2004).
   PubMedGoogle Scholar
• Singleton AB, Farrer M, Johnson J et al. α-synuclein locus triplication causes Parkinson’s disease. Science302(5646), 841 (2003).
   PubMed Web of Science ®Google Scholar
• Fuchs J, Nilsson C, Kachergus J et al. Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication. Neurology68(12), 916–922 (2007).
   PubMed Web of Science ®Google Scholar
• Huang X, Chen PC, Poole C. APOE-ε2 allele associated with higher prevalence of sporadic Parkinson disease. Neurology62(12), 2198–2202 (2004).
   PubMed Web of Science ®Google Scholar
• Li YJ, Hauser MA, Scott WK et al. Apolipoprotein E controls the risk and age at onset of Parkinson disease. Neurology62(11), 2005–2009 (2004).
   PubMed Web of Science ®Google Scholar
• Christensen PM, Gotzsche PC, Brosen K. The sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of Parkinson’s disease: a meta-analysis. Pharmacogenetics8(6), 473–479 (1998).
   PubMedGoogle Scholar
• Tan EK, Khajavi M, Thornby JI, Nagamitsu S, Jankovic J, Ashizawa T. Variability and validity of polymorphism association studies in Parkinson’s disease. Neurology55(4), 533–538 (2000).
   PubMed Web of Science ®Google Scholar
• Benmoyal-Segal L, Soreq H. Gene–environment interactions in sporadic Parkinson’s disease. J. Neurochem.97(6), 1740–1755 (2006).
   PubMedGoogle Scholar
• Maraganore DM, de Andrade M, Elbaz A et al. Collaborative analysis of α-synuclein gene promoter variability and Parkinson disease. JAMA296(6), 661–670 (2006).
   PubMed Web of Science ®Google Scholar
• Evangelou E, Maraganore DM, Ioannidis JP. Meta-analysis in genome-wide association datasets: strategies and application in Parkinson disease. PLoS ONE2, e196 (2007).
   Google Scholar
• Dawn TM, Barrett JH. Genetic linkage studies. Lancet366(9490), 1036–1044 (2005).
   PubMedGoogle Scholar
• Mizuta I, Satake W, Nakabayashi Y et al. Multiple candidate gene analysis identifies α-synuclein as a susceptibility gene for sporadic Parkinson’s disease. Hum. Mol. Genet.15(7), 1151–1158 (2006).
   PubMed Web of Science ®Google Scholar
• Pardo LM, van Duijn CM. In search of genes involved in neurodegenerative disorders. Mutat. Res.592(1,2), 89–101 (2005).
   PubMedGoogle Scholar
• Moore DJ. Parkin: a multifaceted ubiquitin ligase. Biochem. Soc. Trans.34(Part 5), 749–753 (2006).
   PubMed Web of Science ®Google Scholar
• Vigouroux S, Briand M, Briand Y. Linkage between the proteasome pathway and neurodegenerative diseases and aging. Mol. Neurobiol.30(2), 201–221 (2004).
   PubMed Web of Science ®Google Scholar
• Mukaetova-Ladinska EB, McKeith IG. Pathophysiology of synuclein aggregation in Lewy body disease. Mech. Ageing Dev.127(2), 188–202 (2006).
   PubMedGoogle Scholar
• Cookson MR. The biochemistry of Parkinson’s disease. Annu. Rev. Biochem.74, 29–52 (2005).
   PubMed Web of Science ®Google Scholar
• Maries E, Dass B, Collier TJ, Kordower JH, Steece-Collier K. The role of α-synuclein in Parkinson’s disease: insights from animal models. Nat. Rev. Neurosci.4(9), 727–738 (2003).
   PubMed Web of Science ®Google Scholar
• Dawson TM, Dawson VL. Rare genetic mutations shed light on the pathogenesis of Parkinson disease. J. Clin. Invest.111(2), 145–151 (2003).
   PubMed Web of Science ®Google Scholar
• Chartier-Harlin MC, Kachergus J, Roumier C et al. α-synuclein locus duplication as a cause of familial Parkinson’s disease. Lancet364(9440), 1167–1169 (2004).
   PubMed Web of Science ®Google Scholar
• Ferreon AC, Deniz AA. α-synuclein multistate folding thermodynamics: implications for protein misfolding and aggregation. Biochemistry46(15), 4499–4509 (2007).
   PubMedGoogle Scholar
• Martinez Z, Zhu M, Han S, Fink AL. GM1 specifically interacts with α-synuclein and inhibits fibrillation. Biochemistry46(7), 1868–1877 (2007).
   PubMed Web of Science ®Google Scholar
• Chandra S, Gallardo G, Fernandez-Chacon R, Schluter OM, Sudhof TC. α-synuclein cooperates with CSPα in preventing Neurodegeneration Cell123(3), 383–396 (2005).
   PubMed Web of Science ®Google Scholar
• Sung JY, Lee HJ, Jeong EI et al. α-synuclein overexpression reduces gap junctional intercellular communication in dopaminergic neuroblastoma cells. Neurosci. Lett.416(3), 289–293 (2007).
   PubMedGoogle Scholar
• Maingay M, Romero-Ramos M, Kirik D. Viral vector mediated overexpression of human α-synuclein in the nigrostriatal dopaminergic neurons: a new model for Parkinson’s disease. CNS Spectr.10(3), 235–244 (2005).
   PubMedGoogle Scholar
• Mochizuki H, Yamada M, Mizuno Y. α-synuclein overexpression model. J. Neural Transm.70(Suppl.), 281–284 (2006).
   Google Scholar
• Eslamboli A, Romero-Ramos M, Burger C et al. Long-term consequences of human α-synuclein overexpression in the primate ventral midbrain. Brain130(Pt 3), 799–815 (2007).
   PubMed Web of Science ®Google Scholar
• Perez RG, Waymire JC, Lin E, Liu JJ, Guo F, Zigmond MJ. A role for α-synuclein in the regulation of dopamine biosynthesis. J. Neurosci.22(8), 3090–3099 (2002).
   PubMed Web of Science ®Google Scholar
• Abeliovich A, Schmitz Y, Farinas I et al. Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron25(1), 239–252 (2000).
   PubMed Web of Science ®Google Scholar
• Chandra S, Fornai F, Kwon HB et al. Double-knockout mice for α- and β-synucleins: effect on synaptic functions. Proc. Natl Acad. Sci. USA101(41), 14966–14971 (2004).
   PubMed Web of Science ®Google Scholar
• Sidhu A, Wersinger C, Moussa CE, Vernier P. The role of α-synuclein in both neuroprotection and neurodegeneration. Ann. NY Acad. Sci.1035(1), 250–270 (2004).
   PubMed Web of Science ®Google Scholar
• Orth M, Tabrizi SJ. Models of Parkinson’s disease. Mov. Disord.18(7), 729–737 (2003).
   PubMed Web of Science ®Google Scholar
• Cappai R, Leck SL, Tew DJ et al. Dopamine promotes α-synuclein aggregation into SDS-resistant soluble oligomers via a distinct folding pathway. FASEB J.19(10), 1377–1379 (2005).
   PubMed Web of Science ®Google Scholar
• Miller DW, Hague SM, Clarimon J et al. α-synuclein in blood and brain from familial Parkinson disease with SNCA locus triplication. Neurology62(10), 1835–1838 (2004).
   PubMed Web of Science ®Google Scholar
• Fujiwara H, Hasegawa M, Dohmae N et al. α-synuclein is phosphorylated in synucleinopathy lesions. Nat. Cell Biol.4(2), 160–164 (2002).
   PubMed Web of Science ®Google Scholar
• Arawaka S, Wada M, Goto S et al. The role of G-protein-coupled receptor kinase 5 in pathogenesis of sporadic Parkinson’s disease. J. Neurosci.26(36), 9227–9238 (2006).
   PubMed Web of Science ®Google Scholar
• Takahashi M, Uchikado H, Caprotti D et al. Identification of G-protein coupled receptor kinase 2 in paired helical filaments and neurofibrillary tangles. J. Neuropathol. Exp. Neurol.65(12), 1157–1169 (2006).
   PubMed Web of Science ®Google Scholar
• Giasson BI, Duda JE, Murray IV et al. Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions. Science290(5493), 985–989 (2000).
   PubMed Web of Science ®Google Scholar
• Duda JE, Giasson BI, Chen Q et al. Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies. Am. J. Pathol.157(5), 1439–1445 (2000).
   PubMed Web of Science ®Google Scholar
• Paxinou E, Chen Q, Weisse M et al. Induction of α-synuclein aggregation by intracellular nitrative insult. J. Neurosci.21(20), 8053–8061 (2001).
   PubMed Web of Science ®Google Scholar
• Mishizen-Eberz AJ, Norris EH, Giasson BI et al. Cleavage of α-synuclein by calpain: potential role in degradation of fibrillized and nitrated species of α-synuclein. Biochemistry44(21), 7818–7829 (2005).
   PubMedGoogle Scholar
• Lashuel HA, Hartley D, Petre BM, Walz T, Lansbury PT Jr. Neurodegenerative disease: amyloid pores from pathogenic mutations. Nature418(6895), 291 (2002).
   PubMed Web of Science ®Google Scholar
• Tsigelny IF, Bar-On P, Sharikov Y et al. Dynamics of α-synuclein aggregation and inhibition of pore-like oligomer development by β-synuclein. FEBS J.274(7), 1862–1877 (2007).
   PubMed Web of Science ®Google Scholar
• Chen Q, Thorpe J, Keller JN. α-synuclein alters proteasome function, protein synthesis, and stationary phase viability. J. Biol. Chem.280(34), 30009–30017 (2005).
   PubMed Web of Science ®Google Scholar
• Marx FP, Soehn AS, Berg D et al. The proteasomal subunit S6 ATPase is a novel synphilin-1 interacting protein – implications for Parkinson’s disease. FASEB J.21, 1759–1767 (2007).
   PubMed Web of Science ®Google Scholar
• Dekker MC, Bonifati V, van Duijn CM. Parkinson’s disease: piecing together a genetic jigsaw. Brain126(Pt 8), 1722–1733 (2003).
   PubMedGoogle Scholar
• Lohmann E, Periquet M, Bonifati V et al. How much phenotypic variation can be attributed to parkin genotype? Ann. Neurol.54(2), 176–185 (2003).
   PubMed Web of Science ®Google Scholar
• Yamamura Y, Hattori N, Matsumine H, Kuzuhara S, Mizuno Y. Autosomal recessive early-onset parkinsonism with diurnal fluctuation: clinicopathologic characteristics and molecular genetic identification. Brain Dev.22(Suppl. 1), S87–S91 (2000).
   Google Scholar
• Oliveira SA, Scott WK, Martin ER et al. Parkin mutations and susceptibility alleles in late-onset Parkinson’s disease. Ann. Neurol.53(5), 624–629 (2003).
   PubMed Web of Science ®Google Scholar
• Scott WK, Nance MA, Watts RL et al. Complete genomic screen in Parkinson disease: evidence for multiple genes. JAMA286(18), 2239–2244 (2001).
   PubMed Web of Science ®Google Scholar
• Kay DM, Moran D, Moses L et al. Heterozygous parkin point mutations are as common in control subjects as in Parkinson’s patients. Ann. Neurol.61(1), 47–54 (2007).
   PubMed Web of Science ®Google Scholar
• Shimura H, Hattori N, Kubo S et al. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet.25(3), 302–305 (2000).
   PubMed Web of Science ®Google Scholar
• Sakata E, Yamaguchi Y, Kurimoto E et al. Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin-like domain. EMBO Rep.4(3), 301–306 (2003).
   PubMed Web of Science ®Google Scholar
• Zhang Y, Gao J, Chung KK, Huang H, Dawson VL, Dawson TM. Parkin functions as an E2-dependent ubiquitin-protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc. Natl Acad. Sci. USA97(24), 13354–13359 (2000).
   PubMed Web of Science ®Google Scholar
• Imai Y, Soda M, Inoue H, Hattori N, Mizuno Y, Takahashi R. An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell105(7), 891–902 (2001).
   PubMed Web of Science ®Google Scholar
• Ren Y, Zhao J, Feng J. Parkin binds to α/β tubulin and increases their ubiquitination and degradation. J. Neurosci.23(8), 3316–3324 (2003).
   PubMed Web of Science ®Google Scholar
• Yang F, Jiang Q, Zhao J, Ren Y, Sutton MD, Feng J. Parkin stabilizes microtubules through strong binding mediated by three independent domains. J. Biol. Chem.280(17), 17154–17162 (2005).
   PubMed Web of Science ®Google Scholar
• Corti O, Hampe C, Koutnikova H et al. The p38 subunit of the aminoacyl-tRNA synthetase complex is a Parkin substrate: linking protein biosynthesis and neurodegeneration. Hum. Mol. Genet.12(12), 1427–1437 (2003).
   PubMed Web of Science ®Google Scholar
• Tsai YC, Fishman PS, Thakor NV, Oyler GA. Parkin facilitates the elimination of expanded polyglutamine proteins and leads to preservation of proteasome function. J. Biol. Chem.278(24), 22044–22055 (2003).
   PubMed Web of Science ®Google Scholar
• Huynh DP, Scoles DR, Nguyen D, Pulst SM. The autosomal recessive juvenile Parkinson disease gene product, parkin, interacts with and ubiquitinates synaptotagmin XI. Hum. Mol. Genet.12(20), 2587–2597 (2003).
   PubMed Web of Science ®Google Scholar
• Staropoli JF, McDermott C, Martinat C, Schulman B, Demireva E, Abeliovich A. Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity. Neuron37(5), 735–749 (2003).
   PubMed Web of Science ®Google Scholar
• Ko HS, Kim SW, Sriram SR, Dawson VL, Dawson TM. Identification of far upstream element-binding protein-1 as an authentic Parkin substrate. J. Biol. Chem.281(24), 16193–16196 (2006).
   PubMed Web of Science ®Google Scholar
• Chung KK, Zhang Y, Lim KL et al. Parkin ubiquitinates the α-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Nat. Med.7(10), 1144–1150 (2001).
   PubMed Web of Science ®Google Scholar
• Shimura H, Schlossmacher MG, Hattori N et al. Ubiquitination of a new form of α-synuclein by parkin from human brain: implications for Parkinson’s disease. Science293(5528), 263–269 (2001).
   PubMed Web of Science ®Google Scholar
• Kalia SK, Lee S, Smith PD et al. BAG5 inhibits parkin and enhances dopaminergic neuron degeneration. Neuron44(6), 931–945 (2004).
   PubMed Web of Science ®Google Scholar
• Fallon L, Moreau F, Croft BG, Labib N, Gu WJ, Fon EA. Parkin and CASK/LIN-2 associate via a PDZ-mediated interaction and are co-localized in lipid rafts and postsynaptic densities in brain. J. Biol. Chem.277(1), 486–491 (2002).
   PubMedGoogle Scholar
• Fallon L, Belanger CM, Corera AT et al. A regulated interaction with the UIM protein Eps15 implicates parkin in EGF receptor trafficking and PI(3)K-Akt signalling. Nat. Cell Biol.8(8), 834–842 (2006).
   PubMed Web of Science ®Google Scholar
• Farrer M, Chan P, Chen R et al. Lewy bodies and parkinsonism in families with parkin mutations. Ann. Neurol.50(3), 293–300 (2001).
   PubMed Web of Science ®Google Scholar
• Dawson TM. Parkin and defective ubiquitination in Parkinson’s disease. J. Neural Transm.70(Suppl.), 209–213 (2006).
   Google Scholar
• Kahns S, Kalai M, Jakobsen LD, Clark BF, Vandenabeele P, Jensen PH. Caspase-1 and caspase-8 cleave and inactivate cellular parkin. J. Biol. Chem.278(26), 23376–23380 (2003).
   PubMedGoogle Scholar
• Wang C, Ko HS, Thomas B et al. Stress-induced alterations in parkin solubility promote parkin aggregation and compromise parkin’s protective function. Hum. Mol. Genet.14(24), 3885–3897 (2005).
   PubMed Web of Science ®Google Scholar
• Hampe C, Ardila-Osorio H, Fournier M, Brice A, Corti O. Biochemical analysis of Parkinson’s disease-causing variants of Parkin, an E3 ubiquitin-protein ligase with monoubiquitylation capacity. Hum. Mol. Genet.15(13), 2059–2075 (2006).
   PubMed Web of Science ®Google Scholar
• Wong ES, Tan JM, Wang C et al. Relative sensitivity of parkin and other cysteine-containing enzymes to stress-induced solubility alterations. J. Biol. Chem.282(16), 12310–12318 (2007).
   PubMedGoogle Scholar
• Liu Y, Fallon L, Lashuel HA, Liu Z, Lansbury PT Jr. The UCH-L1 gene encodes two opposing enzymatic activities that affect α-synuclein degradation and Parkinson’s disease susceptibility. Cell111(2), 209–218 (2002).
   PubMed Web of Science ®Google Scholar
• Levecque C, Destee A, Mouroux V et al. No genetic association of the ubiquitin carboxy-terminal hydrolase-L1 gene S18Y polymorphism with familial Parkinson’s disease. J. Neural Transm.108(8–9), 979–984 (2001).
   PubMedGoogle Scholar
• Satoh J, Kuroda Y. A polymorphic variation of serine to tyrosine at codon 18 in the ubiquitin C-terminal hydrolase-L1 gene is associated with a reduced risk of sporadic Parkinson’s disease in a Japanese population. J. Neurol. Sci.189(1–2), 113–117 (2001).
   PubMedGoogle Scholar
• Nishikawa K, Li H, Kawamura R et al. Alterations of structure and hydrolase activity of parkinsonism-associated human ubiquitin carboxyl-terminal hydrolase L1 variants. Biochem. Biophys. Res. Commun.304(1), 176–183 (2003).
   PubMedGoogle Scholar
• Cuervo AM. Autophagy: many paths to the same end. Mol. Cell Biochem.263(1–2), 55–72 (2004).
   PubMed Web of Science ®Google Scholar
• Massey AC, Zhang C, Cuervo AM. Chaperone-mediated autophagy in aging and disease. Curr. Top. Dev. Biol.73205–73235 (2006).
   Google Scholar
• Menzies FM, Ravikumar B, Rubinsztein DC. Protective roles for induction of autophagy in multiple proteinopathies. Autophagy2(3), 224–225 (2006).
   PubMed Web of Science ®Google Scholar
• Rubinsztein DC, DiFiglia M, Heintz N et al. Autophagy and its possible roles in nervous system diseases, damage and repair. Autophagy1(1), 11–22 (2005).
   PubMed Web of Science ®Google Scholar
• Stefanis L, Larsen KE, Rideout HJ, Sulzer D, Greene LA. Expression of A53T mutant but not wild-type α-synuclein in PC12 cells induces alterations of the ubiquitin-dependent degradation system, loss of dopamine release, and autophagic cell death. J. Neurosci.21(24), 9549–9560 (2001).
   PubMed Web of Science ®Google Scholar
• Cuervo AM, Stefanis L, Fredenburg R, Lansbury PT, Sulzer D. Impaired degradation of mutant α-synuclein by chaperone-mediated autophagy. Science305(5688), 1292–1295 (2004).
   PubMed Web of Science ®Google Scholar
• Bandhyopadhyay U, Cuervo AM. Chaperone-mediated autophagy in aging and neurodegeneration: Lessons from α-synuclein. Exp. Gerontol.42(1–2), 120–128 (2007).
   PubMedGoogle Scholar
• Andersen JK. Oxidative stress in neurodegeneration: cause or consequence? Nat. Med.10(Suppl.), S18–S25 (2004).
   PubMed Web of Science ®Google Scholar
• Bonifati V, Rizzu P, van Baren MJ et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science299(5604), 256–259 (2003).
   PubMed Web of Science ®Google Scholar
• Kubo S, Hattori N, Mizuno Y. Recessive Parkinson’s disease. Mov. Disord.21(7), 885–893 (2006).
   PubMed Web of Science ®Google Scholar
• Bandopadhyay R, Kingsbury AE, Cookson MR et al. The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson’s disease. Brain127(Pt 2), 420–430 (2004).
   PubMed Web of Science ®Google Scholar
• Olzmann JA, Brown K, Wilkinson KD et al. Familial Parkinson’s disease-associated L166P mutation disrupts DJ-1 protein folding and function. J. Biol. Chem.279(9), 8506–8515 (2004).
   PubMed Web of Science ®Google Scholar
• Zhou W, Zhu M, Wilson MA, Petsko GA, Fink AL. The oxidation state of DJ-1 regulates its chaperone activity toward α-synuclein. J. Mol. Biol.356(4), 1036–1048 (2006).
   PubMed Web of Science ®Google Scholar
• Kim RH, Smith PD, Aleyasin H et al. Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. Proc. Natl Acad. Sci. USA102(14), 5215–5220 (2005).
   PubMed Web of Science ®Google Scholar
• Canet-Aviles RM, Wilson MA, Miller DW et al. The Parkinson’s disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proc. Natl Acad. Sci. USA101(24), 9103–9108 (2004).
   PubMed Web of Science ®Google Scholar
• Kinumi T, Kimata J, Taira T, Ariga H, Niki E. Cysteine-106 of DJ-1 is the most sensitive cysteine residue to hydrogen peroxide-mediated oxidation in vivo in human umbilical vein endothelial cells. Biochem. Biophys. Res. Commun.317(3), 722–728 (2004).
   PubMed Web of Science ®Google Scholar
• Moore DJ, Zhang L, Troncoso J et al. Association of DJ-1 and parkin mediated by pathogenic DJ-1 mutations and oxidative stress. Hum. Mol. Genet.14(1), 71–84 (2005).
   PubMed Web of Science ®Google Scholar
• Borrelli E. Without DJ-1, the D2 receptor doesn’t play. Neuron45(4), 479–481 (2005).
   PubMedGoogle Scholar
• Valente EM, Bentivoglio AR, Dixon PH et al. Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35–p36. Am. J. Hum. Genet.68(4), 895–900 (2001).
   PubMed Web of Science ®Google Scholar
• Valente EM, Abou-Sleiman PM, Caputo V et al. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science304(5674), 1158–1160 (2004).
   PubMed Web of Science ®Google Scholar
• Tan JM, Dawson TM. Parkin blushed by PINK1. Neuron50(4), 527–529 (2006).
   PubMedGoogle Scholar
• Muqit MM, Abou-Sleiman PM, Saurin AT et al. Altered cleavage and localization of PINK1 to aggresomes in the presence of proteasomal stress. J. Neurochem.98(1), 156–169 (2006).
   PubMed Web of Science ®Google Scholar
• Park J, Lee SB, Lee S et al. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature441(7097), 1157–1161 (2006).
   PubMed Web of Science ®Google Scholar
• Yang Y, Gehrke S, Imai Y et al. Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc. Natl Acad. Sci. USA103(28), 10793–10798 (2006).
   PubMed Web of Science ®Google Scholar
• Singleton A. What does PINK1 mean for Parkinson diseases? Neurology63(8), 1350–1351 (2004).
   PubMedGoogle Scholar
• Strauss KM, Martins LM, Plun-Favreau H et al. Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson’s disease. Hum. Mol. Genet.14(15), 2099–2111 (2005).
   PubMed Web of Science ®Google Scholar
• Abou-Sleiman PM, Muqit MM, Wood NW. Expanding insights of mitochondrial dysfunction in Parkinson’s disease. Nat. Rev. Neurosci.7(3), 207–219 (2006).
   PubMed Web of Science ®Google Scholar
• Schapira AH. Mitochondrial disease. Lancet368(9529), 70–82 (2006).
   PubMed Web of Science ®Google Scholar
• Bolton JL, Trush MA, Penning TM, Dryhurst G, Monks TJ. Role of quinones in toxicology. Chem. Res. Toxicol.13(3), 135–160 (2000).
   PubMed Web of Science ®Google Scholar
• Cavalieri EL, Rogan EG, Chakravarti D. Initiation of cancer and other diseases by catechol ortho-quinones: a unifying mechanism. Cell. Mol. Life Sci.59(4), 665–681 (2002).
   PubMed Web of Science ®Google Scholar
• Cavalieri EL, Li KM, Balu N et al. Catechol ortho-quinones: the electrophilic compounds that form depurinating DNA adducts and could initiate cancer and other diseases. Carcinogenesis23(6), 1071–1077 (2002).
   PubMed Web of Science ®Google Scholar
• Fitzmaurice PS, Ang L, Guttman M, Rajput AH, Furukawa Y, Kish SJ. Nigral glutathione deficiency is not specific for idiopathic Parkinson’s disease. Mov. Disord.18(9), 969–976 (2003).
   PubMedGoogle Scholar
• Cohen G. Oxidative stress, mitochondrial respiration, and Parkinson’s disease. Ann. NY Acad. Sci.899, 112–120 (2000).
   PubMedGoogle Scholar
• Shults CW. Mitochondrial dysfunction and possible treatments in Parkinson’s disease – a review. Mitochondrion4(5–6), 641–648 (2004).
   PubMed Web of Science ®Google Scholar
• Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR. Iron, brain ageing and neurodegenerative disorders. Nat. Rev. Neurosci.5(11), 863–873 (2004).
   PubMed Web of Science ®Google Scholar
• Floor E. Iron as a vulnerability factor in nigrostriatal degeneration in aging and Parkinson’s disease. Cell. Mol. Biol. (Noisy-le-grand)46(4), 709–720 (2000).
   PubMed Web of Science ®Google Scholar
• Zhu BT. On the mechanism of homocysteine pathophysiology and pathogenesis: a unifying hypothesis. Histol. Histopathol.17(4), 1283–1291 (2002).
   PubMedGoogle Scholar
• Zhu BT. Catechol-O-Methyltransferase (COMT)-mediated methylation metabolism of endogenous bioactive catechols and modulation by endobiotics and xenobiotics: importance in pathophysiology and pathogenesis. Curr. Drug Metab.3(3), 321–349 (2002).
   PubMed Web of Science ®Google Scholar
• Etminan M, Gill SS, Samii A. Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson’s disease: a meta-analysis. Lancet Neurol.4(6), 362–365 (2005).
   PubMed Web of Science ®Google Scholar
• Muller T, Buttner T, Gholipour AF, Kuhn W. Coenzyme Q10 supplementation provides mild symptomatic benefit in patients with Parkinson’s disease. Neurosci. Lett.341(3), 201–204 (2003).
   PubMed Web of Science ®Google Scholar
• Storch A, Jost WH, Vieregge P et al. Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q10 in Parkinson disease. Arch. Neurol.64, 938–944 (2007).
   PubMed Web of Science ®Google Scholar
• Whitton PS. Inflammation as a causative factor in the aetiology of Parkinson’s disease. Br. J. Pharmacol.150(8), 963–976 (2007).
   PubMed Web of Science ®Google Scholar
• Kim YS, Joh TH. Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson’s disease. Exp Mol Med.38(4), 333–347 (2006).
   PubMed Web of Science ®Google Scholar
• Sawada M, Imamura K, Nagatsu T. Role of cytokines in inflammatory process in Parkinson’s disease. J. Neural Transm. Suppl.70, 373–381 (2006).
   PubMedGoogle Scholar
• Gao HM, Jiang J, Wilson B, Zhang W, Hong JS, Liu B. Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson’s disease. J. Neurochem.81(6), 1285–1297 (2002).
   PubMed Web of Science ®Google Scholar
• Gao HM, Hong JS, Zhang W, Liu B. Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide: relevance to the etiology of Parkinson’s disease. J. Neurosci.23(4), 1228–1236 (2003).
   PubMed Web of Science ®Google Scholar
• Zhang W, Qin L, Wang T et al. 3-hydroxymorphinan is neurotrophic to dopaminergic neurons and is also neuroprotective against LPS-induced neurotoxicity. FASEB J.19(3), 395–397 (2005).
   PubMedGoogle Scholar
• Ahlskog JE. Challenging conventional wisdom: the etiologic role of dopamine oxidative stress in Parkinson’s disease. Mov. Disord.20(3), 271–282 (2005).
   PubMedGoogle Scholar
• Mancuso C, Scapagini G, Curro D et al. Mitochondrial dysfunction, free radical generation and cellular stress response in neurodegenerative disorders. Front. Biosci.121107–121123 (2007).
   Google Scholar
• Funayama M, Hasegawa K, Ohta E et al. An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family. Ann. Neurol.57(6), 918–921 (2005).
   PubMed Web of Science ®Google Scholar
• Whaley NR, Uitti RJ, Dickson DW, Farrer MJ, Wszolek ZK. Clinical and pathologic features of families with LRRK2-associated Parkinson’s disease. J. Neural Transm. Suppl.70, 221–229 (2006).
   PubMedGoogle Scholar
• Hatano T, Kubo S, Imai S et al. Leucine-rich repeat kinase 2 associates with lipid rafts. Hum. Mol. Genet.16(6), 678–690 (2007).
   PubMed Web of Science ®Google Scholar
• Biskup S, Moore DJ, Celsi F et al. Localization of LRRK2 to membranous and vesicular structures in mammalian brain. Ann. Neurol.60(5), 557–569 (2006).
   PubMed Web of Science ®Google Scholar
• West AB, Moore DJ, Biskup S et al. Parkinson’s disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc. Natl Acad. Sci. USA102(46), 16842–16847 (2005).
   PubMed Web of Science ®Google Scholar
• Galter D, Westerlund M, Carmine A, Lindqvist E, Sydow O, Olson L. LRRK2 expression linked to dopamine-innervated areas. Ann. Neurol.59(4), 714–719 (2006).
   PubMed Web of Science ®Google Scholar
• Taymans JM, Van den Haute C, Baekelandt V. Distribution of PINK1 and LRRK2 in rat and mouse brain. J. Neurochem.98(3), 951–961 (2006).
   PubMed Web of Science ®Google Scholar
• White LR, Toft M, Kvam SN, Farrer MJ, Aasly JO. MAPK-pathway activity, Lrrk2 G2019S, and Parkinson’s disease. J. Neurosci. Res.85(6), 1288–1294 (2007).
   PubMed Web of Science ®Google Scholar
• Miklossy J, Arai T, Guo JP et al. LRRK2 expression in normal and pathologic human brain and in human cell lines. J. Neuropathol. Exp. Neurol.65(10), 953–963 (2006).
   PubMed Web of Science ®Google Scholar
• Giasson BI, Covy JP, Bonini NM et al. Biochemical and pathological characterization of LRRK2. Ann. Neurol.59(2), 315–322 (2006).
   PubMedGoogle Scholar
• Higashi S, Biskup S, West AB et al. Localization of Parkinson’s disease-associated LRRK2 in normal and pathological human brain. Brain Res.1155, 208–219 (2007).
   PubMed Web of Science ®Google Scholar
• Mata IF, Wedemeyer WJ, Farrer MJ, Taylor JP, Gallo KA. LRRK2 in Parkinson’s disease: protein domains and functional insights. Trends Neurosci.29(5), 286–293 (2006).
   PubMed Web of Science ®Google Scholar
• Paisan-Ruiz C, Jain S, Evans EW et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron44(4), 595–600 (2004).
   PubMed Web of Science ®Google Scholar
• Ito G, Okai T, Fujino G et al. GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson’s disease. Biochemistry46(5), 1380–1388 (2007).
   PubMed Web of Science ®Google Scholar
• Smith WW, Pei Z, Jiang H et al. Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. Proc. Natl Acad. Sci. USA102(51), 18676–18681 (2005).
   PubMed Web of Science ®Google Scholar
• Jaleel M, Nichols RJ, Deak M et al. LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson’s disease mutants affect kinase activity. Biochem. J.405(2), 307–317 (2007).
   PubMedGoogle Scholar
• Gloeckner CJ, Kinkl N, Schumacher A et al. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. Hum. Mol. Genet.15(2), 223–232 (2006).
   PubMed Web of Science ®Google Scholar
• Schapira AH. The importance of LRRK2 mutations in Parkinson disease. Arch. Neurol.63(9), 1225–1228 (2006).
   PubMedGoogle Scholar
• Olanow CW, Jankovic J. Neuroprotective therapy in Parkinson’s disease and motor complications: a search for a pathogenesis-targeted, disease-modifying strategy. Mov. Disord.20(Suppl. 11), S3–S10 (2005).
   PubMedGoogle Scholar
• Parkinson Study Group. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA287(13), 1653–1661 (2002).
   PubMed Web of Science ®Google Scholar
• Whone AL, Watts RL, Stoessl AJ et al. Slower progression of Parkinson’s disease with ropinirole versus levodopa: the REAL-PET study. Ann. Neurol.54(1), 93–101 (2003).
   PubMed Web of Science ®Google Scholar
• Fahn S, Oakes D, Shoulson I et al. Levodopa and the progression of Parkinson’s disease. N. Engl. J. Med.351(24), 2498–2508 (2004).
   PubMed Web of Science ®Google Scholar
• Shoulson I. DATATOP: a decade of neuroprotective inquiry. Parkinson study group. deprenyl and tocopherol antioxidative therapy of parkinsonism. Ann. Neurol.44(3 Suppl. 1), S160–S166 (1998).
   PubMed Web of Science ®Google Scholar
• Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Arch. Neurol.59(12), 1937–1943 (2002).
   PubMed Web of Science ®Google Scholar
• Hara MR, Thomas B, Cascio MB et al. Neuroprotection by pharmacologic blockade of the GAPDH death cascade. Proc. Natl Acad. Sci. USA103(10), 3887–3889 (2006).
   PubMed Web of Science ®Google Scholar
• Hallett PJ, Standaert DG. Rationale for and use of NMDA receptor antagonists in Parkinson’s disease. Pharmacol. Ther.102(2), 155–174 (2004).
   PubMed Web of Science ®Google Scholar
• Jankovic J, Hunter C. A double-blind, placebo-controlled and longitudinal study of riluzole in early Parkinson’s disease. Parkinsonism Relat. Disord.8(4), 271–276 (2002).
   PubMed Web of Science ®Google Scholar
• Kordower JH, Emborg ME, Bloch J et al. Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson’s disease. Science290(5492), 767–773 (2000).
   PubMed Web of Science ®Google Scholar
• Nutt JG, Burchiel KJ, Comella CL et al. Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology60(1), 69–73 (2003).
   PubMed Web of Science ®Google Scholar
• Patel NK, Bunnage M, Plaha P, Svendsen CN, Heywood P, Gill SS. Intraputamenal infusion of glial cell line-derived neurotrophic factor in PD: a two-year outcome study. Ann. Neurol.57(2), 298–302 (2005).
   PubMed Web of Science ®Google Scholar
• Lang AE, Gill S, Patel NK et al. Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease. Ann. Neurol.59(3), 459–466 (2006).
   PubMed Web of Science ®Google Scholar
• Bespalov MM, Saarma M. GDNF family receptor complexes are emerging drug targets. Trends Pharmacol. Sci.28(2), 68–74 (2007).
   PubMed Web of Science ®Google Scholar
• Ahn M, Kim S, Kang M, Ryu Y, Kim TD. Chaperone-like activities of αsynuclein: α-synuclein assists enzyme activities of esterases. Biochem. Biophys. Res. Commun.346(4), 1142–1149 (2006).
   PubMed Web of Science ®Google Scholar
• Winklhofer KF, Tatzelt J. The role of chaperones in Parkinson’s disease and prion diseases. Handb. Exp. Pharmacol.172, 221–258 (2006).
   Google Scholar
• Gregersen N. Protein misfolding disorders: pathogenesis and intervention. J. Inherit. Metab. Dis.29(2–3), 456–470 (2006).
   PubMed Web of Science ®Google Scholar
• Snyder BJ, Olanow CW. Stem cell treatment for Parkinson’s disease: an update for 2005. Curr. Opin. Neurol.18(4), 376–385 (2005).
   PubMed Web of Science ®Google Scholar
• Kaplitt MG, Feigin A, Tang C et al. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson’s disease: an open label, Phase I trial. Lancet369(9579), 2097–2105 (2007).
   PubMed Web of Science ®Google Scholar
• Gilgun-Sherki Y, Djaldetti R, Melamed E, Offen D. Polymorphism in candidate genes: implications for the risk and treatment of idiopathic Parkinson’s disease. Pharmacogenomics J.4(5), 291–306 (2004).
   PubMedGoogle Scholar
• Acuna G, Foernzler D, Leong D et al. Pharmacogenetic analysis of adverse drug effect reveals genetic variant for susceptibility to liver toxicity. Pharmacogenomics J.2(5), 327–334 (2002).
   PubMedGoogle Scholar
• Arbouw ME, van Vugt JP, Egberts TC, Guchelaar HJ. Pharmacogenetics of antiparkinsonian drug treatment: a systematic review. Pharmacogenomics8(2), 159–176 (2007).
   PubMed Web of Science ®Google Scholar
• Farrer MJ. Genetics of Parkinson disease: paradigm shifts and future prospects. Nat. Rev. Genet.7(4), 306–318 (2006).
   PubMed Web of Science ®Google Scholar
• Schapira AH, Bezard E, Brotchie J et al. Novel pharmacological targets for the treatment of Parkinson’s disease. Nat. Rev. Drug Discov.5(10), 845–854 (2006).
   PubMed Web of Science ®Google Scholar
• Hattori N, Mizuno Y. Pathogenetic mechanisms of parkin in Parkinson’s disease. Lancet364(9435), 722–724 (2004).
   PubMed Web of Science ®Google Scholar
• Huang Y, Cheung L, Rowe D, Halliday G. Genetic contributions to Parkinson’s disease. Brain Res. Brain Res. Rev.46(1), 44–70 (2004).
   PubMedGoogle Scholar
• Park J, Lee SB, Lee S et al. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature441(7097), 1157–1161 (2006).
   PubMed Web of Science ®Google Scholar
• Yang Y, Gehrke S, Imai Y et al. Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc. Natl Acad. Sci. USA103(28), 10793–10798 (2006).
   PubMed Web of Science ®Google Scholar
• Naidu Y, Chaudhuri KR. Transdermal rotigotine: a new non-ergot dopamine agonist for the treatment of Parkinson’s disease. Expert Opin. Drug Deliv.4(2), 111–118 (2007).
   PubMed Web of Science ®Google Scholar
• Olanow CW, Agid Y, Mizuno Y et al. Levodopa in the treatment of Parkinson’s disease: current controversies. Mov. Disord.19(9), 997–1005 (2004).
   PubMed Web of Science ®Google Scholar
• Uc EY, Follett KA. Deep brain stimulation in movement disorders. Semin. Neurol.27(2), 170–182 (2007).
   PubMedGoogle Scholar
• Gan J, Xie-Brustolin J, Mertens P et al. Bilateral subthalamic nucleus stimulation in advanced Parkinson’s disease: three years follow-up. J Neurol254(1), 99–106 (2007).
   PubMedGoogle Scholar