Early diagnosis and therapy of Parkinson’s disease: can disease progression be curbed?

Anderson JP, Walker DE, Goldstein JM et al (2006) Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J Biol Chem 281:29739–29752

Ara J, Przedborski S, Naini AB et al (1998) Inactivation of tyrosine hydroxylase by nitration following exposure to peroxynitrite and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Proc Natl Acad Sci USA 95:7659–7663

Bar-Am O, Weinreb O, Amit T, Youdim MBH (2010) The neuroprotective mechanism of 1-(R)-aminoindan, the major metabolite of the anti-parkinsonian drug rasagiline. J Neurochem 112:1131–1137

Baratchi S, Kanwar RK, Kanwar JR (2010) Survivin: a target from brain cancer to neurodegenerative disease. Crit Rev Biochem Mol Biol 45:535–554

Barone P (2011) Treatment of depressive symptoms in Parkinson’s disease. Eur J Neurol 18:11–15

Bartus RT, Brown L, Wilson A, Kruegel B et al (2011a) Properly scaled and targeted AAV2-NRTN (neurturin) to the substantia nigra is safe, effective and causes no weight loss: support for nigral targeting in Parkinson’s disease. Neurobiol Dis 44(1):38–52

Bartus RT, Herzog CD, Chu Y et al (2011b) Bioactivity of AAV2-neurturin gene therapy (CERE-120): differences between Parkinson’s disease and nonhuman primate brains. Mov Disord 26(1):27–36

Bennett EJ, Bence NF, Jayakumar R, Kopito RR (2005) Global impairment of the ubiquitin-proteasome system by nuclear or cytoplasmic protein aggregates precedes inclusion body formation. Mol Cell 17:351–365

Berg D, Hochstrasser H, Schweitzer KJ, Riess O (2006) Disturbance of iron metabolism in Parkinson’s disease ultrasonography as a biomarker. Neurotox Res 9:1–13

Bilsland J, Roy S, Xanthoudakis S et al (2002) Caspase inhibitors attenuate 1-methyl-4-phenylpyridinium toxicity in primary cultures of mesencephalic dopaminergic neurons. J Neurosci 22:2637–2649

Braak H, Del Tredici K (2008) Invited Article: nervous system pathology in sporadic Parkinson disease. Neurology 70(20):1916–1925

Braga CA, Follmer C, Palhano FL et al (2011) The anti-Parkinsonian drug selegiline delays the nucleation phase of alpha-synuclein aggregation leading to the formation of nontoxic species. J Mol Biol 405:254–273

Chaudhuri K, Healy D, Schapira A et al (2006) Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol 5(3):235–245

Chen Y, Harvey B, Hoffman A et al (2008) MPTP-induced deficits in striatal synaptic plasticity are prevented by glial cell line-derived neurotrophic factor expressed via an adeno-associated viral vector. FASEB J 22:261–275

Conn KJ, Gao WW, McKee A et al (2004) Identification of the protein disulfide isomerase family member PDIp in experimental Parkinson’s disease and Lewy body pathology. Brain Res 1022:164–172

Cook C, Petrucelli L (2009) A critical evaluation of the ubiquitin-proteasome system in Parkinson’s disease. Mol Basis Dis 1792:664–675

Corrigan MH, Denahan AQ, Wright CE et al (2000) Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. Depress Anxiety J 11:58–65

Coune PG, Schneider BL, Aebischer P (2012) Parkinson’s disease: gene therapies. Cold Spring Harb Perspect Med 2(4):a009431

de la Fuente-Fernandez R, Schulzer M, Kuramoto L et al (2011) Age-specific progression of nigrostriatal dysfunction in Parkinson’s disease. Ann Neurol 69:803–810

Dev KK, Hofele K, Barbieri S et al (2003) Part II: alpha-synuclein and its molecular pathophysiological role in neurodegenerative disease. Neuropharmacology 45:14–44

Double KL, Rowe DB, Carew-Jones FM et al (2009) Anti-melanin antibodies are increased in sera in Parkinson’s disease. Exp Neurol 217:297–301

Dusek P, Jankovic J, Le W (2012) Iron dysregulation in movement disorders. Neurobiol Dis 46(1):1–18

Egawa N, Yamamoto K, Inoue H et al (2011) The endoplasmic reticulum stress sensor, ATF6 alpha, protects against neurotoxin-induced dopaminergic neuronal death. J Biol Chem 286:7947–7957

El-Agnaf OMA, Salem SA, Paleologou K et al (2006) Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson’s disease. FASEB J 20:419–425

Emre M, Aarsland D, Albanese A (2004) Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med 351:2509–2518

Fitzgerald JC, Plun-Favreau H (2008) Emerging pathways in genetic Parkinson’s disease: autosomal-recessive genes in Parkinson’s disease—a common pathway? FEBS J 275:5758–5766

Follett KA, Torres-Russotto D (2012) Deep brain stimulation of globus pallidus interna, subthalamic nucleus, and pedunculopontine nucleus for Parkinson’s disease: which target? Parkinsonism Relat Disord 18(Suppl 1):S165–S167

Fujiwara H, Hasegawa M, Dohmae N et al (2002) alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol 4:160–164

Fukumitsu N, Suzuki M, Fukuda T, Kiyono Y (2009) Multipoint analysis of reduced (125)I-meta-iodobenzylguanidine uptake and norepinephrine turnover in the hearts of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine-induced parkinsonism. Nucl Med Biol 36:623–629

Gal S, Zheng H, Fridkin M, Youdim MB (2010) Restoration of nigrostriatal dopamine neurons in post-MPTP treatment by the novel multifunctional brain-permeable iron chelator-monoamine oxidase inhibitor drug, M30. Neurotox Res 17:15–27

Gallagher CL, Oakes TR, Johnson SC et al (2011) Rate of 6-[18F]fluorodopa uptake decline in striatal subregions in Parkinson’s disease. Mov Disord 26:614–620

Gautier CA, Kitada T, Shen J (2008) Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. Proc Natl Acad Sci USA 105:11364–11369

Haehner A, Boesveldt S, Berendse HW et al (2009) Prevalence of smell loss in Parkinson’s disease—a multicenter study. Parkinsonism Relat Disord 15:490–494

Hart RG, Pearce LA, Ravina BM et al (2009) Neuroprotection trials in Parkinson’s disease: systematic review. Mov Disord 24:647–654

Hartmann A, Hunot S, Michel PP (2000) Caspase-3: a vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson’s disease. Proc Natl Acad Sci USA 97:2875–2880

Haynes CM, Titus EA, Cooper AA (2004) Degradation of misfolded proteins prevents ER-derived oxidative stress and cell death. Mol Cell 15:767–776

Hirsch EC, Breidert T, Rousselet E et al (2003) The role of glial reaction and inflammation in Parkinson’s disease. Ann N Y Acad Sci 991:214–228

Hirsch EC, Hunot S, Hartmann A (2005) Neuroinflammatory processes in Parkinson’s disease. Parkinsonism Relat Disord 11(Suppl 1):S9–S15

Holford NHG, Nutt JG (2011) Interpreting the results of Parkinson’s disease clinical trials: time for a change. Mov Disord 26:569–577

Irrcher I, Aleyasin H, Seifert EL et al (2010) Loss of the Parkinson’s disease-linked gene DJ-1 perturbs mitochondrial dynamics. Hum Mol Genet 19:3734–3746

Jankovic J, Chen S, Le W (2005) The role of Nurr1 in the development of dopaminergic neurons and Parkinson’s disease. Prog Neurobiol 77:128–138

Jiang HB, Wu YC, Nakamura M et al (2007) Parkinson’s disease genetic mutations increase cell susceptibility to stress: mutant alpha-synuclein enhances H2O2- and Sin-1-induced cell death. Neurobiol Aging 28:1709–1717

Jourdi H, Hamo L, Oka T et al (2009) BDNF mediates the neuroprotective effects of positive AMPA receptor modulators against MPP(+)-induced toxicity in cultured hippocampal and mesencephalic slices. Neuropharmacology 56:876–885

Junn E, Lee KW, Jeong BS et al (2009) Repression of alpha-synuclein expression and toxicity by microRNA-7. Proc Natl Acad Sci USA 106:13052–13057

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

Klegeris A, Pelech S, Giasson BI et al (2008) Alpha-synuclein activates stress signaling protein kinases in THP-1 cells and microglia. Neurobiol Aging 29:739–752

Klein C, Westenberger A (2012) Genetics of Parkinson’s disease. Cold Spring Harb Perspect Med. doi: 10.1101/cshperspect.a008888

Klein C, Hagenah J, Landwehrmeyer B et al (2011) The presymptomatic stage of neurodegenerative disorders. Nervenarzt 82(8):994–1001

Kooncumchoo P, Sharma S, Porter J et al (2006) Coenzyme Q(10) provides neuroprotection in iron-induced apoptosis in dopaminergic neurons. J Mol Neurosci 28:125–141

Kruger R, Kuhn W, Muller T, Woitalla D et al (1998) Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson’s disease. Nat Genet 18:106–108

Kupershmidt L, Weinreb O, Amit T et al (2011) Novel molecular targets of the neuroprotective/neurorescue multimodal iron chelating drug M30 in the mouse brain. Neuroscience 189:345–358

Lang AE (2010) Clinical trials of disease-modifying therapies for neurodegenerative diseases: the challenges and the future. Nature Med 16:1223–1226

Lang AE (2011) A critical appraisal of the premotor symptoms of Parkinson’s disease: potential usefulness in early diagnosis and design of neuroprotective trials. Mov Disord 26:775–783

Le W, Pan T, Huang M, Xu P (2008) Decreased NURR1 gene expression in patients with Parkinson’s disease. J Neurol Sci 273:29–33

Le W, Nguyena D, Lina XW et al (2011) Transcription factor PITX3 gene in Parkinson’s disease. Neurobiol Aging 32(4):750–753

Lemke MR, Brecht HM, Koester J, Reichmann H (2006) Effects of the dopamine agonist pramipexole on depression, anhedonia and motor functioning in Parkinson’s disease. J Neurol Sci 248:266–270

Lesage S, Durr A, Tazir M et al (2006) LRRK2 G2019S as a cause of Parkinson’s disease in North African Arabs. N Engl J Med 354:422–423

Lin X, Parisiadou L, Gu XL et al (2009) Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson’s-disease-related mutant alpha-synuclein. Neuron 64:807–827

Lin CH, Tsai PI, Wu RM et al (2010) LRRK2 G2019S mutation induces dendrite degeneration through mislocalization and phosphorylation of tau by recruiting autoactivated GSK3 beta. J Neurosci 30:13138–13149

Martin WRW, Wieler M, Gee M (2008) Midbrain iron content in early Parkinson disease: a potential biomarker of disease status. Neurology 70:1411–1417

Martinat C, Bacci JJ, Leete T et al (2006) Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype. Proc Natl Acad Sci USA 103:2874–2879

Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM et al (2011) The impact of non-motor symptoms on health-related quality of life of patients with Parkinson’s disease. Mov Disord J 26:399–406

Masliah E, Rockenstein E, Mante M et al (2011) Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease. PLoS One 6:e19338

Meissner WG, Frasier M, Gasser T et al (2011) Priorities in Parkinson’s disease research. Nat Rev Drug Discov 10:377–393

Meixner A, Boldt K, Van Troys M, et al (2011) A QUICK screen for Lrrk2 partners—leucine-rich repeat kinase 2 is involved in actin cytoskeleton dynamics. Mol Cell Proteomics 10. doi: 10.1074/mcp.M110.001172

Murer MG, Yan Q, Raisman-Vozari R (2001) Brain-derived neurotrophic factor in the control human brain, and in Alzheimer’s disease and Parkinson’s disease. Prog Neurobiol 63:71–124

Nagatsu T, Sawada M (2005) Inflammatory process in Parkinson’s disease: role for cytokines. Curr Pharm Des 11:999–1016

Naoi M, Maruyama W (2010) Monoamine oxidase inhibitors as neuroprotective agents in age-dependent neurodegenerative disorders. Curr Pharm Des 16:2799–2817

Nussbaum RL, Ellis CE (2003) Alzheimer’s disease and Parkinson’s disease. N Engl J Med 348:1356–1364

Olanow CW, Rascol O, Hauser R et al (2009) A double-blind, delayed-start trial of Rasagiline in Parkinson’s disease. N Engl J Med 361:1268–1278

Ozelius LJ, Senthil G, Saunders-Pullman R et al (2006) LRRK2 G2019S as a cause of Parkinson’s disease in Ashkenazi Jews. N Engl J Med 354:424–425

Panzacchi A, Moresco RM, Garibotto V et al (2008) A voxel-based PET study of dopamine transporters in Parkinson’s disease: relevance of age at onset. Neurobiol Dis 31:102–109

Pavese N, Brooks DJ (2009) Imaging neurodegeneration in Parkinson’s disease. Mol Basis Dis 1792:722–729

Peng J, Xie L, Stevenson FF et al (2006) Nigrostriatal dopaminergic neurodegeneration in the weaver mouse is mediated via neuroinflammation and alleviated by minocycline administration. J Neurosci 26:11644–11651

Peng C, Aron L, Klein R et al (2011) Pitx3 is a critical mediator of GDNF-induced BDNF expression in nigrostriatal dopaminergic neurons. J Neurosci 31(36):12802–12815

Periquet M, Morwena L, Lohmann E et al (2003) Parkin mutations are frequent in patients with isolated early onset parkinsonism. Brain 126:1271–1278

Pizzolato G, Mandat T (2012) Deep brain stimulation for movement disorders. Front Integr Neurosci 6:2

Polymeropoulos MH, Lavedan C, Leroy E et al (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276:2045–2047

Ramonet D, Daher JPL, Lin BM et al (2011) Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2. PLoS One 6:e18568

Rangasamy SB, Soderstrom K, Bakay RA, Kordower JH (2010) Neurotrophic factor therapy for Parkinson’s disease. Prog Brain Res 184:237–264

Ravina B, Kieburtz K, Tilley B et al (2006) A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology 66:664–671

Riederer P, Laux G (2011) MAO-inhibitors in Parkinson’s disease. Exp Neurobiol 20:1–17

Ros-Bernal F, Hunot S, Herrero MT et al (2011) Microglial glucocorticoid receptors play a pivotal role in regulating dopaminergic neurodegeneration in parkinsonism. Proc Natl Acad Sci USA 108:6632–6637

Salsone M, Bagnato A, Novellino F et al (2009) Cardiac MIBG scintigraphy in primary progressive freezing gait. Parkinsonism Relat Disord 15:365–369

Satake W, Nakabayashi Y, Mizuta I et al (2009) Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson’s disease. Nat Genet 41:1303–1308

Schimmel JJ, Crews L, Roffler-Tarlov S, Chikaraishi DM (1999) 4.5 kb of the rate tyrosine hydroxylase 5′ flanking sequence directs tissue specific expression during development and contains consensus sites for multiple transcription factors. Mol Brain Res 74:1–14

Schneeberger A, Mandler M, Mattner F et al (2012) Vaccination for Parkinson’s disease. Parkinsonism Relat Disord 18:S11–S13

Sian-Hülsmann J, Mandel S, Youdim MB, Riederer P (2011) The relevance of iron in the pathogenesis of Parkinson’s disease. J Neurochem 118:939–957

Singleton AB, Farrer M, Johnson J et al (2003) Alpha-synuclein locus triplication causes Parkinson’s disease. Science 302:841

Snow AD, Cummings J, Hudson M et al (2009) Development of Synuclere: a novel small molecule that effectively reduces brain alpha-synuclein aggregation and improves motor dysfunction. Mov Disord 24:S251

Snow BJ, Rolfe FL, Lockhart MM et al (2010) A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson’s disease. Mov Disord 25:1670–1674

Stowe R, Ives N, Clarke CE, Deane K et al (2010) Evaluation of the efficacy and safety of adjuvant treatment to levodopa therapy in Parkinson’s disease patients with motor complications. Cochrane Database Syst Rev 7:CD007166

Swistowski A, Peng J, Liu QY et al (2010) Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions. Stem Cells 28:1893–1904

Tan EK, Yew K, Chua E et al (2006) PINK1 mutations in sporadic early-onset Parkinson’s disease. Mov Disord 21:789–793

Tang B, Xiong H, Sun P et al (2006) Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson’s disease. Hum Mol Genet 15:1816–1825

Tong YR, Yamaguchi H, Giaime E et al (2010) Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of alpha-synuclein, and apoptotic cell death in aged mice. Proc Natl Acad Sci USA 107:9879–9884

Tykocki T, Mandat T, Nauman P (2011) Pedunculopontine nucleus deep brain stimulation in Parkinson’s disease. Arch Med Sci 7(4):555–564

Valente EM, Abou-Sleiman PM, Caputo V et al (2004) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304:1158–1160

Varrone A, Marek KL, Jennings D et al (2001) [123I]β-CIT SPECT imaging demonstrates reduced density of striatal dopamine transporters in Parkinson’s disease and multiple system atrophy. Mov Disord 16:1023–1032

Voon V, Fernagut PO, Wickens J et al (2009) Chronic dopaminergic stimulation in Parkinson’s disease: from dyskinesias to impulse control disorders. Lancet Neurol 8:1140–1149

Waragai M, Wei J, Fujita M et al (2006) Increased level of DJ-1 in the cerebrospinal fluids of sporadic Parkinson’s disease. Biochem Biophys Res Commun 345:967–972

Weinreb O, Amit T, Bar-Am O et al (2010) A novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity. Prog Neurobiol 92:330–344

West AB, Moore DJ, Biskup S et al (2005) Parkinson’s disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci USA 102:16842–16847

Witt K, Daniels C, Reiff J, Krack P et al (2008) Neuropsychological and psychiatric changes after deep brain stimulation for Parkinson’s disease: a randomised, multicentre study. Lancet Neurol 7:605–614

Wu YC, Le W, Jankovic J (2011) Preclinical biomarkers of Parkinson disease. Arch Neurol 68(1):22–30

Yanamandra K, Gruden MA, Casaite V et al (2011) Alpha-synuclein reactive antibodies as diagnostic biomarkers in blood sera of Parkinson’s disease patients. PLoS One 6:e18513

Zarranz JJ, Alegre J, Gomez-Esteban JC et al (2004) The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 55:164–173

Zesiewicz TA, Sullivan KL, Arnulf I et al (2010) Practice parameter: treatment of nonmotor symptoms of Parkinson disease. Neurology 74:924–931

Zhu W, Xie W, Pan T et al (2007) Prevention and rescue of lactacystin induced nigrostriatal dopamine neurons degeneration by novel brain permeable iron chelators. FASEB J 21:3835–3844

Zhu W, Xie W, Pan T et al (2008) Comparison of neuroprotective and neurorestorative capabilities of rasagiline and selegiline against lactacystin-induced nigrostriatal dopaminergic degeneration. J Neurochem 105(5):1970–1978

Zhu W, Li XP, Xie WJ et al (2010) Genetic iron chelation protects against proteasome inhibition-induced dopamine neuron degeneration. Neurobiol Dis 37:307–313