Aktuelle Neurologie 2014; 41(10): 573-578
DOI: 10.1055/s-0034-1387475
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Ursache der Parkinson-Krankheit: Braak revisited

Aetiology of Parkinson's Disease: Braak revisited
F. J. Pan-Montojo
1   Neurologische Klinik und Poliklinik, Klinikum der Universität München
,
H. Reichmann
2   Klinik und Poliklinik für Neurologie, Klinikum Carl Gustav Carus, Dresden
› Author Affiliations
Further Information

Publication History

Publication Date:
08 January 2015 (online)

Zusammenfassung

Bewegungsstörungen gehören zu den komplizierten neurologischen Krankheiten. Ihre Ursachen sind nur z. T. bekannt und vermutlich multifaktoriell. Die Behandlung der meisten Bewegungsstörungen bezieht sich nur auf die Symptome und hat z. T. erhebliche Nebenwirkungen. Morbus Parkinson (MP) bzw. das idiopathische Parkinson-Syndrom (IPS) ist die häufigste Bewegungsstörungskrankheit und die zweithäufigste neurodegenerative Krankheit nach Morbus Alzheimer. Sie ist langsam progredient und betrifft mehrere Regionen des zentralen und peripheren Nervensystems. In diesem Artikel wollen wir eine Übersicht der letzten Studien geben und davon ableiten, dass die jüngsten Erkenntnisse zur Krankheitsprogression durch alpha-Synuklein zu einer neuen nahezu kausalen Therapie führen könnten.

Abstract

Movement disorders belong to the most complicated neurodegenerative diseases. The aetiology of these disorders is only partially understood and most probably multi-factorial. The treatment in these cases is normally restricted to the symptoms and has many side effects. Parkinson's disease is the most frequent movement disorder and the second most frequent neurodegenerative disease after Alzheimerʼs disease. It is slowly progressive and affects different regions from the central and peripheral nervous systems. In this review, we would like to give the reader an overview of the latest studies done in this field. We believe that the new findings regarding the role of alpha-synuclein in the progression of Parkinsonʼs disease will lead to new, more specific causal therapies.

 
  • Literatur

  • 1 Checkoway H, Nelson LM. Epidemiologic approaches to the study of Parkinson’s disease etiology. Epidemiology 1999; 10: 327-336
  • 2 Twelves D, Perkins KS, Counsell C. Systematic review of incidence studies of Parkinson’s disease. Mov Disord 2003; 18: 19-31
  • 3 de Rijk MC, Launer LJ, Berger K et al. Prevalence of Parkinson’s disease in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 2000; 54: S21-23
  • 4 Gasser T. Genetics of Parkinson’s disease. Clin Genet 1998; 54: 259-265
  • 5 Bekris LM, Mata IF, Zabetian CP. The genetics of Parkinson disease. J Geriatr Psychiatry Neurol 2010; 23: 228-242
  • 6 Ben-Shlomo Y. The epidemiology of Parkinson’s disease. Baillieres Clin Neurol 1997; 6: 55-68
  • 7 Tanner CM, Ben-Shlomo Y. Epidemiology of Parkinson’s disease. Advances Neurol 1999; 80: 153-159
  • 8 Baldi I, Cantagrel A, Lebailly P et al. Association between Parkinson’s disease and exposure to pesticides in southwestern France. Neuroepidemiology 2003; 22: 305-310
  • 9 Freire C, Koifman S. Pesticide exposure and Parkinson’s disease: epidemiological evidence of association. Neurotoxicology 2012; 33: 947-971
  • 10 Gorell JM, Johnson CC, Rybicki BA et al. The risk of Parkinson’s disease with exposure to pesticides, farming, well water, and rural living. Neurology 1998; 50: 1346-1350
  • 11 Kamel F, Tanner C, Umbach D et al. Pesticide exposure and self-reported Parkinson’s disease in the agricultural health study. Am J Epidemiol 2007; 165: 364-374
  • 12 Rajput AH, Uitti RJ, Stern W et al. Early onset Parkinson’s disease in Saskatchewan – environmental considerations for etiology. Can J Neurol Sci 1986; 13: 312-316
  • 13 Behari M, Srivastava AK, Das RR et al. Risk factors of Parkinson’s disease in Indian patients. J Neurol Sci 2001; 190: 49-55
  • 14 Liou HH, Tsai MC, Chen CJ et al. Environmental risk factors and Parkinson’s disease: a case-control study in Taiwan. Neurology 1997; 48: 1583-1588
  • 15 Seidler A, Hellenbrand W, Robra BP et al. Possible environmental, occupational, and other etiologic factors for Parkinson’s disease: a case-control study in Germany. Neurology 1996; 46: 1275-1284
  • 16 Semchuk KM, Love EJ, Lee RG. Parkinson’s disease and exposure to agricultural work and pesticide chemicals. Neurology 1992; 42: 1328-1335
  • 17 Tanner CM, Kamel F, Ross GW et al. Rotenone, paraquat, and Parkinson’s disease. Environ Health Perspect 2011; 119: 866-872
  • 18 Priyadarshi A, Khuder SA, Schaub EA et al. Environmental risk factors and Parkinson’s disease: a metaanalysis. Environ Res 2001; 86: 122-127
  • 19 Lai BC, Marion SA, Teschke K et al. Occupational and environmental risk factors for Parkinson’s disease. Parkinsonism Relat Disord 2002; 8: 297-309
  • 20 Doder M, Jahanshahi M, Turjanski N et al. Parkinson’s syndrome after closed head injury: a single case report. J Neurol Neurosurg Psychiatry 1999; 66: 380-385
  • 21 Nayernouri T. Posttraumatic parkinsonism. Surg Neurol 1985; 24: 263-264
  • 22 Goldman SM, Tanner CM, Oakes D et al. Head injury and Parkinson’s disease risk in twins. Ann Neurol 2006; 60: 65-72
  • 23 Jafari S, Etminan M, Aminzadeh F et al. Head injury and risk of Parkinson disease: a systematic review and meta-analysis. Mov Disord 2013; 28: 1222-1229
  • 24 Liu B, Hong JS. Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther 2003; 304: 1-7
  • 25 Ghaemi M, Rudolf J, Schmulling S et al. FDG- and Dopa-PET in postencephalitic parkinsonism. J Neural Transm 2000; 107: 1289-1295
  • 26 Abbott RD, Petrovitch H, White LR et al. Frequency of bowel movements and the future risk of Parkinson’s disease. Neurology 2001; 57: 456-462
  • 27 Baron JA. Cigarette smoking and Parkinson’s disease. Neurology 1986; 36: 1490-1496
  • 28 Ascherio A, Zhang SM, Hernan MA et al. Prospective study of caffeine consumption and risk of Parkinson’s disease in men and women. Ann Neurol 2001; 50: 56-63
  • 29 Weisskopf MG, O’Reilly E, Chen H et al. Plasma urate and risk of Parkinson’s disease. Am J Epidemiol 2007; 166: 561-567
  • 30 Forno LS. Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol 1996; 55: 259-272
  • 31 Spillantini MG, Schmidt ML, Lee VM et al. Alpha-synuclein in Lewy bodies. Nature 1997; 388: 839-840
  • 32 Braak H, Del Tredici K, Rub U et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003; 24: 197-211
  • 33 Braak H, Ghebremedhin E, Rub U et al. Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 2004; 318: 121-134
  • 34 Wakabayashi K, Takahashi H. Neuropathology of autonomic nervous system in Parkinson’s disease. Eur Neurol 1997; 38 (Suppl. 02) 2-7
  • 35 Braak H, de Vos RA, Bohl J et al. Gastric alpha-synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology. Neurosci Lett 2006; 396: 67-72
  • 36 Del Tredici K, Hawkes CH, Ghebremedhin E et al. Lewy pathology in the submandibular gland of individuals with incidental Lewy body disease and sporadic Parkinson’s disease. Acta Neuropathol 2010; 119: 703-713
  • 37 Orimo S, Amino T, Itoh Y et al. Cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy body disease. Acta Neuropathol 2005; 109: 583-588
  • 38 Wolters E, Braak H. Parkinson’s disease: premotor clinico-pathological correlations. J Neural Transm Suppl 2006; 70: 309-319
  • 39 Shulman LM, Taback RL, Bean J et al. Comorbidity of the nonmotor symptoms of Parkinson’s disease. Mov Disord 2001; 16: 507-510
  • 40 Chaudhuri KR, Martinez-Martin P. Quantitation of non-motor symptoms in Parkinson’s disease. Eur J Neurol 2008; 15 (Suppl. 02) 2-7
  • 41 Haehner A, Hummel T, Hummel C et al. Olfactory loss may be a first sign of idiopathic Parkinson’s disease. Mov Disord 2007; 22: 839-842
  • 42 Sommer U, Hummel T, Cormann K et al. Detection of presymptomatic Parkinson’s disease: combining smell tests, transcranial sonography, and SPECT. Mov Disord 2004; 19: 1196-1202
  • 43 Ponsen MM, Stoffers D, Wolters E et al. Olfactory testing combined with dopamine transporter imaging as a method to detect prodromal Parkinson’s disease. J Neurol Neurosurg Psychiatry 2010; 81: 396-399
  • 44 Stiasny-Kolster K, Doerr Y, Moller JC et al. Combination of ‘idiopathic’ REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain 2005; 128: 126-137
  • 45 Fleming L, Mann JB, Bean J et al. Parkinson’s disease and brain levels of organochlorine pesticides. Ann Neurol 1994; 36: 100-103
  • 46 Manning-Bog AB, McCormack AL, Li J et al. The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein. J Biol Chem 2002; 277: 1641-1644
  • 47 Alam M, Schmidt WJ. Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats. Behav Brain Res 2002; 136: 317-324
  • 48 Uversky VN, Li J, Fink AL. Pesticides directly accelerate the rate of alpha-synuclein fibril formation: a possible factor in Parkinson’s disease. FEBS Lett 2001; 500: 105-108
  • 49 Huang CC, Lu CS, Chu NS et al. Progression after chronic manganese exposure. Neurology 1993; 43: 1479-1483
  • 50 Needleman H, Landrigan PJ. Toxins at the pump. New York Times 1996; 15
  • 51 Richardson JR, Roy A, Shalat SL et al. beta-Hexachlorocyclohexane levels in serum and risk of Parkinson’s disease. Neurotoxicology 2011; 32: 640-645
  • 52 Champy P, Hoglinger GU, Feger J et al. Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats: possible relevance for atypical parkinsonism in Guadeloupe. J Neurochem 2004; 88: 63-69
  • 53 Betarbet R, Sherer TB, MacKenzie G et al. Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 2000; 3: 1301-1306
  • 54 Hoeglinger GU, Feger J, Prigent A et al. Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats. J Neurochem 2003; 84: 491-502
  • 55 Pan-Montojo F, Anichtchik O, Dening Y et al. Progression of Parkinson’s disease pathology is reproduced by intragastric administration of rotenone in mice. PLoS One 2010; 5: e8762
  • 56 Pan-Montojo F, Schwarz M, Winkler C et al. Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice. Scientific Rep 2012; 2: 898
  • 57 Desplats P, Lee HJ, Bae EJ et al. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci U S A 2009; 106: 13010-13015
  • 58 Li JY, Englund E, Holton JL et al. Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat Med 2008; 14: 501-503
  • 59 Angot E, Steiner JA, Lema Tome CM et al. Alpha-Synuclein Cell-to-Cell Transfer and Seeding in Grafted Dopaminergic Neurons In Vivo. PLoS One 2012; 7: e39465
  • 60 Luk KC, Kehm V, Carroll J et al. Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 2012; 338: 949-953
  • 61 Braidy N, Gai WP, Xu YH et al. Alpha-Synuclein Transmission and Mitochondrial Toxicity in Primary Human Foetal Enteric Neurons In Vitro. Neurotox Res 2014; 25: 170-182
  • 62 Klegeris A, Giasson BI, Zhang H et al. Alpha-synuclein and its disease-causing mutants induce ICAM-1 and IL-6 in human astrocytes and astrocytoma cells. FASEB J 2006; 20: 2000-2008
  • 63 Valente EM, Salvi S, Ialongo T et al. PINK1 mutations are associated with sporadic early-onset parkinsonism. Ann Neurol 2004; 56: 336-341
  • 64 Esteves AR, Arduino DM, Silva DF et al. Mitochondrial Dysfunction: The Road to Alpha-Synuclein Oligomerization in PD. Parkinsons Dis 2011; 2011: 693-761
  • 65 Freeman D, Cedillos R, Choyke S et al. Alpha-synuclein induces lysosomal rupture and cathepsin dependent reactive oxygen species following endocytosis. PLoS One 2013; 8: e62143
  • 66 Chinta SJ, Mallajosyula JK, Rane A et al. Mitochondrial alpha-synuclein accumulation impairs complex I function in dopaminergic neurons and results in increased mitophagy in vivo. Neurosci Lett 2010; 486: 235-239
  • 67 Braidy N, Gai WP, Xu YH et al. Alpha-synuclein transmission and mitochondrial toxicity in primary human foetal enteric neurons in vitro. Neurotox Res 2014; 25: 170-182
  • 68 Gao HM, Kotzbauer PT, Uryu K et al. Neuroinflammation and oxidation/nitration of alpha-synuclein linked to dopaminergic neurodegeneration. J Neurosci 2008; 28: 7687-7698
  • 69 Gao HM, Zhang F, Zhou H et al. Neuroinflammation and alpha-synuclein dysfunction potentiate each other, driving chronic progression of neurodegeneration in a mouse model of Parkinson’s disease. Environm Health Perspect 2011; 119: 807-814
  • 70 Frank-Cannon TC, Tran T, Ruhn KA et al. Parkin deficiency increases vulnerability to inflammation-related nigral degeneration. J Neurosci 2008; 28: 10825-10834
  • 71 Norris EH, Uryu K, Leight S et al. Pesticide exposure exacerbates alpha-synucleinopathy in an A53T transgenic mouse model. Am J Pathol 2007; 170: 658-666
  • 72 Manning-Bog AB, McCormack AL, Purisai MG et al. Alpha-synuclein overexpression protects against paraquat-induced neurodegeneration. J Neurosci 2003; 23: 3095-3099
  • 73 Kahle PJ, Waak J, Gasser T. DJ-1 and prevention of oxidative stress in Parkinson’s disease and other age-related disorders. Free radical biology & medicine 2009; 47: 1354-1361
  • 74 Masliah E, Dumaop W, Galasko D et al. Distinctive patterns of DNA methylation associated with Parkinson disease: identification of concordant epigenetic changes in brain and peripheral blood leukocytes. Epigenetics 2013; 8: 1030-1038
  • 75 Iacobazzi V, Castegna A, Infantino V et al. Mitochondrial DNA methylation as a next-generation biomarker and diagnostic tool. Mol Genet Metabol 2013; 110: 25-34
  • 76 Marques S, Outeiro TF. Epigenetics in Parkinson’s and Alzheimer’s diseases. Sub-cell Biochem 2013; 61: 507-525
  • 77 Zhu M, Han S, Fink AL. Oxidized quercetin inhibits alpha-synuclein fibrillization. Biochim Biophys Acta 2013; 1830: 2872-2881
  • 78 Horvath I, Sellstedt M, Weise C et al. Modulation of alpha-synuclein fibrillization by ring-fused 2-pyridones: templation and inhibition involve oligomers with different structure. Arch Biochem Biophys 2013; 532: 84-90
  • 79 Decressac M, Mattsson B, Weikop P et al. TFEB-mediated autophagy rescues midbrain dopamine neurons from alpha-synuclein toxicity. Proc Natl Acad Sci U S A 2013; 110: E1817-1826
  • 80 Shaltiel-Karyo R, Davidi D, Frenkel-Pinter M et al. Differential inhibition of alpha-synuclein oligomeric and fibrillar assembly in parkinson’s disease model by cinnamon extract. Biochim Biophys Acta 2012; 1820: 1628-1635
  • 81 Lorenzen N, Nielsen SB, Yoshimura Y et al. How Epigallocatechin Gallate Can Inhibit alpha-Synuclein Oligomer Toxicity in Vitro. J Biol Chem 2014; 289: 21299-21310
  • 82 Wagner J, Ryazanov S, Leonov A et al. Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinsonʼs disease. Acta Neuropathol 2013; 125: 795-813
  • 83 Jackrel ME, DeSantis ME, Martinez BA et al. Potentiated Hsp104 variants antagonize diverse proteotoxic misfolding events. Cell 2014; 156: 170-182
  • 84 McLean PJ, Kawamata H, Shariff S et al. TorsinA and heat shock proteins act as molecular chaperones: suppression of alpha-synuclein aggregation. J Neurochem 2002; 83: 846-854
  • 85 Du Y, Wang F, Zou J et al. Histone deacetylase 6 regulates cytotoxic alpha-synuclein accumulation through induction of the heat shock response. Neurobiol Aging 2014; 35: 2316-2328
  • 86 Faria C, Jorge CD, Borges N et al. Inhibition of formation of alpha-synuclein inclusions by mannosylglycerate in a yeast model of Parkinson’s disease. Biochim Biophys Acta 2013; 1830: 4065-4072
  • 87 Games D, Valera E, Spencer B et al. Reducing C-terminal-truncated alpha-synuclein by immunotherapy attenuates neurodegeneration and propagation in Parkinson’s disease-like models. J Neurosci 2014; 34: 9441-9454
  • 88 Spencer B, Emadi S, Desplats P et al. ESCRT-mediated Uptake and Degradation of Brain-targeted alpha-synuclein Single Chain Antibody Attenuates Neuronal Degeneration In Vivo. Mol Ther 2014; 1753-1767
  • 89 Tran HT, Chung CH, Iba M et al. Alpha-synuclein immunotherapy blocks uptake and templated propagation of misfolded alpha-synuclein and neurodegeneration. Cell Rep 2014; 7: 2054-2065
  • 90 Lindstrom V, Fagerqvist T, Nordstrom E et al. Immunotherapy targeting alpha-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P] alpha-synuclein mice. Neurobiol Dis 2014; 69: 134-143
  • 91 Sanchez-Guajardo V, Annibali A, Jensen PH et al. alpha-Synuclein vaccination prevents the accumulation of parkinson disease-like pathologic inclusions in striatum in association with regulatory T cell recruitment in a rat model. J Neuropathol Exp Neurol 2013; 72: 624-645
  • 92 Besong-Agbo D, Wolf E, Jessen F et al. Naturally occurring alpha-synuclein autoantibody levels are lower in patients with Parkinson disease. Neurology 2013; 80: 169-175
  • 93 Janetzky B, Hauck S, Youdim MB et al. Unaltered aconitase activity, but decreased complex I activity in substantia nigra pars compacta of patients with Parkinson’s disease. Neurosci Lett 1994; 169: 126-128
  • 94 Schapira AH. Evidence for mitochondrial dysfunction in Parkinson’s disease – a critical appraisal. Mov Disord 1994; 9: 125-138
  • 95 Menke T, Gille G, Reber F et al. Coenzyme Q10 reduces the toxicity of rotenone in neuronal cultures by preserving the mitochondrial membrane potential. BioFactors 2003; 18: 65-72
  • 96 Sandoval-Acuna C, Ferreira J, Speisky H. Polyphenols and mitochondria: An update on their increasingly emerging ROS-scavenging independent actions. Arch Biochem Biophys 2014; 559C: 75-90
  • 97 Caruana M, Neuner J, Hogen T et al. Polyphenolic compounds are novel protective agents against lipid membrane damage by alpha-synuclein aggregates in vitro. Biochim Biophys Acta 2012; 1818: 2502-2510
  • 98 Geed M, Garabadu D, Ahmad A et al. Silibinin pretreatment attenuates biochemical and behavioral changes induced by intrastriatal MPP+ injection in rats. Pharmal Biochem Behav 2014; 117: 92-103
  • 99 Rousseau E, Michel PP, Hirsch EC. The iron-binding protein lactoferrin protects vulnerable dopamine neurons from degeneration by preserving mitochondrial calcium homeostasis. Mol Pharmacol 2013; 84: 888-898
  • 100 Toyoda Y, Erkut C, Pan-Montojo F et al. Products of the Parkinson’s disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival. Biology open 2014; DOI: 10.1242/bio.20149399.
  • 101 Storch A, Jost WH, Vieregge P et al. Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q(10) in Parkinson disease. Arch Neurol 2007; 64: 938-944