The pathology roadmap in Parkinson disease

Prion

Volumn 7, Issue 1, 2013, Pages 85-91

  Surmeier, D James ^a   Sulzer, David ^b  

^a NORTHWESTERN UNIVERSITY   (United States)

^b Och Spine at New York Presbyterian Hospitals   (United States)

Author keywords

Calcium; Ion channel; Mitochondria; Neuroprotection; Oxidant stress; Parkinson disease

Indexed keywords

ALPHA SYNUCLEIN; LEVODOPA; MITOCHONDRIAL DNA; NEUROMELANIN; NEUROTRANSMITTER; VESICULAR MONOAMINE TRANSPORTER;

AUTONOMIC NERVOUS SYSTEM; CENTRAL NERVOUS SYSTEM; CHOLINERGIC NERVE CELL; CONFERENCE PAPER; DOPAMINERGIC NERVE CELL; EXTRACELLULAR SPACE; HUMAN; LEWY BODY; LOCUS CERULEUS; MOTOR NERVE; NERVE FIBER; PARKINSON DISEASE; PATHOGENESIS; PEDUNCULOPONTINE TEGMENTAL NUCLEUS; PHENOTYPE; SENSORY NERVE; SUBSTANTIA NIGRA PARS COMPACTA; VENTRAL TEGMENTUM;

CALCIUM; ION CHANNEL; MITOCHONDRIA; NEUROPROTECTION; OXIDANT STRESS; PARKINSON'S DISEASE;

ALPHA-SYNUCLEIN; ANIMALS; BRAIN; CALCIUM; HUMANS; MITOCHONDRIA; NEURONS; OXIDATIVE STRESS; PARKINSON DISEASE; SUBSTANTIA NIGRA;

EID: 84874636271     PISSN: 19336896     EISSN: 1933690X     Source Type: Journal    
DOI: 10.4161/pri.23582     Document Type: Conference Paper

References (120)

1. Fahn S, Sulzer D. Neurodegeneration and neuroprotection in Parkinson disease. NeuroRx 2004; 1:139-54; PMID:15717014; http://dx.doi.org/10.1602/ neurorx.1.1.139.
2. Del Tredici K, Braak H. Lewy pathology and neurodegeneration in premotor Parkinson's disease. Mov Disord 2012; 27:597-607; PMID:22508278; http://dx.doi.org/10.1002/mds.24921.
3. Jellinger KA. Neuropathology of sporadic Parkinson's disease: evaluation and changes of concepts. Mov Disord 2012; 27:8-30; PMID:22081500; http://dx.doi.org/10.1002/mds.23795.
4. Braak H, Del Tredici K. Neuroanatomy and pathology of sporadic Parkinson's disease. Adv Anat Embryol Cell Biol 2009; 201:1-119; PMID:19230552.
5. Cersosimo MG, Benarroch EE. Autonomic involvement in Parkinson's disease: Pathology, pathophysiology, clinical features and possible peripheral biomarkers. J Neurol Sci 2011;313: 57-63; PMID:22001247; http://dx.doi.org/10. 1016/j.jns.2011.09.030.
6. Goldstein DS, Holmes CS, Dendi R, Bruce SR, Li ST. Orthostatic hypotension from sympathetic denervation in Parkinson's disease. Neurology 2002; 58:1247- 55; PMID:11971094; http://dx.doi.org/10.1212/WNL.58.8.1247.
7. Orimo S, Uchihara T, Kanazawa T, Itoh Y, Wakabayashi K, Kakita A, et al. Unmyelinated axons are more vulnerable to degeneration than myelinated axons of the cardiac nerve in Parkinson's disease. Neuropathol Appl Neurobiol 2011; 37:791-802; PMID:21696416; http://dx.doi.org/10.1111/j.1365-2990.2011.01194.x.
8. Ghebremedhin E, Del Tredici K, Langston JW, Braak H. Diminished tyrosine hydroxylase immunoreactivity in the cardiac conduction system and myocardium in Parkinson's disease: an anatomical study. Acta Neuropathol 2009; 118:777-84; PMID:19802627; http://dx.doi.org/10.1007/s00401-009-0596-y.
9. Amino T, Orimo S, Itoh Y, Takahashi A, Uchihara T, Mizusawa H. Profound cardiac sympathetic denervation occurs in Parkinson disease. Brain Pathol 2005; 15:29-34; PMID:15779234; http://dx.doi.org/10.1111/j.1750-3639.2005.tb00097.x.
10. Takeda S, Yamazaki K, Miyakawa T, Arai H. Parkinson's disease with involvement of the parasympathetic ganglia. Acta Neuropathol 1993; 86:397- 8; PMID:8256591; http://dx.doi.org/10.1007/BF00369454.
11. Del Tredici K, Hawkes CH, Ghebremedhin E, Braak H. Lewy pathology in the submandibular gland of individuals with incidental Lewy body disease and sporadic Parkinson's disease. Acta Neuropathol 2010; 119:703- 13; PMID:20229352; http://dx.doi.org/10.1007/s00401-010-0665-2.
12. Del Tredici K, Rüb U, De Vos RA, Bohl JR, Braak H. Where does parkinson disease pathology begin in the brain? J Neuropathol Exp Neurol 2002; 61:413-26; PMID:12030260.
13. Djaldetti R, Lev N, Melamed E. Lesions outside the CNS in Parkinson's disease. Mov Disord 2009; 24:793- 800; PMID:19224610; http://dx.doi.org/10.1002/ mds.22172.
14. Miki Y, Tomiyama M, Ueno T, Haga R, Nishijima H, Suzuki C, et al. Clinical availability of skin biopsy in the diagnosis of Parkinson's disease. Neurosci Lett 2010; 469:357-9; PMID:20026177; http://dx.doi.org/10.1016/j. neulet.2009.12.027.
15. Li Z, Chalazonitis A, Huang YY, Mann JJ, Margolis KG, Yang QM, et al. Essential roles of enteric neuronal serotonin in gastrointestinal motility and the development/survival of enteric dopaminergic neurons. J Neurosci 2011; 31:8998-9009; PMID:21677183; http://dx.doi.org/10.1523/JNEUROSCI.6684-10.2011.
16. Wakabayashi K, Takahashi H, Takeda S, Ohama E, Ikuta F. Parkinson's disease: the presence of Lewy bodies in Auerbach's and Meissner's plexuses. Acta Neuropathol 1988; 76:217-21; PMID:2850698; http://dx.doi.org/10.1007/ BF00687767.
17. Anlauf M, Schäfer MK, Eiden L, Weihe E. Chemical coding of the human gastrointestinal nervous system: cholinergic, VIPergic, and catecholaminergic phenotypes. J Comp Neurol 2003; 459:90- 111; PMID:12629668; http://dx.doi.org/ 10.1002/cne.10599.
18. Singaram C, Ashraf W, Gaumnitz EA, Torbey C, Sengupta A, Pfeiffer R, et al. Dopaminergic defect of enteric nervous system in Parkinson's disease patients with chronic constipation. Lancet 1995; 346:861-4; PMID:7564669; http://dx.doi.org/10.1016/S0140-6736(95)92707-7.
19. Lebouvier T, Chaumette T, Paillusson S, Duyckaerts C, Bruley des Varannes S, Neunlist M, et al. The second brain and Parkinson's disease. Eur J Neurosci 2009; 30:735-41; PMID:19712093; http://dx.doi.org/10.1111/j.1460-9568.2009. 06873.x.
20. Gallegos-Orozco JF, Foxx-Orenstein AE, Sterler SM, Stoa JM. Chronic constipation in the elderly. Am J Gastroenterol 2012; 107:18-25, quiz 26; PMID:21989145; http://dx.doi.org/10.1038/ajg.2011.349.
21. Wakabayashi K, Takahashi H, Ohama E, Ikuta F. Parkinson's disease: an immunohistochemical study of Lewy body-containing neurons in the enteric nervous system. Acta Neuropathol 1990; 79:581- 3; PMID:1972853; http://dx.doi.org/10. 1007/BF00294234.
22. Lebouvier T, Neunlist M, Bruley des Varannes S, Coron E, Drouard A, N'Guyen JM, et al. Colonic biopsies to assess the neuropathology of Parkinson's disease and its relationship with symptoms. PLoS One 2010; 5:e12728; PMID:20856865; http://dx.doi.org/10.1371/journal.pone.0012728.
23. Del Tredici K, Braak H. A not entirely benign procedure: progression of Parkinson's disease. Acta Neuropathol 2008; 115:379-84; PMID:18320198; http://dx.doi.org/10.1007/s00401-008-0355-5.
24. Kalaitzakis ME, Graeber MB, Gentleman SM, Pearce RKB. Controversies over the staging of alphasynuclein pathology in Parkinson's disease. Acta Neuropathol 2008; 116:125-8, author reply 129-31; PMID:18446352; http://dx.doi.org/10.1007/ s00401-008-0381-3.
25. Jellinger KA. A critical evaluation of current staging of alpha-synuclein pathology in Lewy body disorders. Biochim Biophys Acta 2009; 1792:730-40; PMID:18718530; http://dx.doi.org/10.1016/j.bbadis.2008.07.006.
26. Gai WP, Blumbergs PC, Geffen LB, Blessing WW. Agerelated loss of dorsal vagal neurons in Parkinson's disease. Neurology 1992; 42:2106-11; PMID:1436519; http://dx.doi.org/10.1212/WNL.42.11.2106.
27. Foix C, Nicolesco J. Cérébrale: Les Noyauz Gris Centraux Et La Région Mésencephalo-Soue-Optique. SuiviD'Un Appendice Sur L'Anatomic Pathologique De La Maladie De Parkinson. (Masson et Cie.: Paris, 1925).
28. Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 2003; 24:197-211; PMID:12498954; http://dx.doi.org/10.1016/S0197-4580(02) 00065-9.
29. Weihe E, Depboylu C, Schütz B, Schäfer MKH, Eiden LE. Three types of tyrosine hydroxylase-positive CNS neurons distinguished by dopa decarboxylase and VMAT2 co-expression. Cell Mol Neurobiol 2006; 26:659-78; PMID:16741673; http://dx.doi.org/10.1007/s10571-006-9053-9.
30. Tretiakoff C. Contribution a l'etude de l'anatomie pathologique du locus niger de Soemmering avec quelques dedutions relatives a la pathogenie des troubles du tonus musculaire et de la maladie de Parkinson. These de Paris 1919.
31. Eadie MJ. The pathology certain medullary nuceli in Parkinsonism. Brain 1963; 86:781-92; PMID:14090529; http://dx.doi.org/10.1093/brain/86.4.781.
32. Saper CB, Sorrentino DM, German DC, de Lacalle S. Medullary catecholaminergic neurons in the normal human brain and in Parkinson's disease. Ann Neurol 1991; 29:577-84; PMID:1892359; http://dx.doi.org/10.1002/ana. 410290602.
33. Greenfield JG, Bosanquet FD. The brain-stem lesions in Parkinsonism. J Neurol Neurosurg Psychiatry 1953; 16:213-26; PMID:13109537; http://dx.doi.org/ 10.1136/jnnp.16.4.213.
34. Halliday GM, Li YW, Blumbergs PC, Joh TH, Cotton RG, Howe PR, et al. Neuropathology of immunohistochemically identified brainstem neurons in Parkinson's disease. Ann Neurol 1990; 27:373-85; PMID:1972319; http://dx.doi.org/10.1002/ana.410270405.
35. Fahn S. Description of Parkinson's disease as a clinical syndrome. Ann N Y Acad Sci 2003; 991:1-14; PMID:12846969; http://dx.doi.org/10.1111/j.1749-6632. 2003.tb07458.x.
36. McRitchie DA, Cartwright HR, Halliday GM. Specific A10 dopaminergic nuclei in the midbrain degenerate in Parkinson's disease. Exp Neurol 1997; 144:202- 13; PMID:9126172; http://dx.doi.org/10.1006/exnr.1997.6418.
37. Hirsch E, Graybiel AM, Agid YA. Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease. Nature 1988; 334:345-8; PMID:2899295; http://dx.doi.org/10.1038/334345a0.
38. Zarow C, Lyness SA, Mortimer JA, Chui HC. Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch Neurol 2003; 60:337-41; PMID:12633144; http://dx.doi.org/10.1001/archneur.60.3.337.
39. Liang CL, Sinton CM, Sonsalla PK, German DC. Midbrain dopaminergic neurons in the mouse that contain calbindin-D28k exhibit reduced vulnerability to MPTP-induced neurodegeneration. Neurodegeneration 1996; 5:313-8; PMID:9117542; http://dx.doi.org/10.1006/neur.1996.0042.
40. Liang CL, Nelson O, Yazdani U, Pasbakhsh P, German DC. Inverse relationship between the contents of neuromelanin pigment and the vesicular monoamine transporter-2: human midbrain dopamine neurons. J Comp Neurol 2004; 473:97-106; PMID:15067721; http://dx.doi.org/10.1002/cne.20098.
41. Damier P, Hirsch EC, Agid Y, Graybiel AM. The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson's disease. Brain 1999; 122:1437-48; PMID:10430830; http://dx.doi.org/10.1093/ brain/122.8.1437.
42. Gai WP, Halliday GM, Blumbergs PC, Geffen LB, Blessing WW. Substance P-containing neurons in the mesopontine tegmentum are severely affected in Parkinson's disease. Brain 1991; 114:2253- 67; PMID:1718530; http://dx.doi.org/10.1093/brain/114.5.2253.
43. Jenkinson N, Nandi D, Muthusamy K, Ray NJ, Gregory R, Stein JF, et al. Anatomy, physiology, and pathophysiology of the pedunculopontine nucleus. Mov Disord 2009; 24:319-28; PMID:19097193; http://dx.doi.org/10.1002/mds.22189.
44. Jellinger K. The pedunculopontine nucleus in Parkinson's disease, progressive supranuclear palsy and Alzheimer's disease. J Neurol Neurosurg Psychiatry 1988; 51:540-3; PMID:3379428; http://dx.doi.org/10.1136/jnnp.51.4. 540.
45. Hirsch EC, Graybiel AM, Duyckaerts C, Javoy-Agid F. Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. Proc Natl Acad Sci U S A 1987; 84:5976- 80; PMID:3475716; http://dx.doi.org/10.1073/pnas.84.16.5976.
46. Ubeda-Bañon I, Saiz-Sanchez D, de la Rosa-Prieto C, Argandoña-Palacios L, Garcia-Muñozguren S, Martinez-Marcos A. alpha-Synucleinopathy in the human olfactory system in Parkinson's disease: involvement of calcium-binding protein- and substance P-positive cells. Acta Neuropathol 2010; 119:723-35; PMID:20383714; http://dx.doi.org/10.1007/s00401- 010-0687-9.
47. Wilson RS, Yu L, Schneider JA, Arnold SE, Buchman AS, Bennett DA. Lewy bodies and olfactory dysfunction in old age. Chem Senses 2011; 36:367-73; PMID:21257733; http://dx.doi.org/10.1093/chemse/bjq139.
48. Pearce RK, Hawkes CH, Daniel SE. The anterior olfactory nucleus in Parkinson's disease. Mov Disord 1995; 10:283-7; PMID:7651444; http://dx.doi.org/10.1002/mds.870100309.
49. Huisman E, Uylings HBM, Hoogland PV. Genderrelated changes in increase of dopaminergic neurons in the olfactory bulb of Parkinson's disease patients. Mov Disord 2008; 23:1407-13; PMID:18581481; http://dx.doi.org/10.1002/mds.22009.
50. Baker H, Liu N, Chun HS, Saino S, Berlin R, Volpe B, et al. Phenotypic differentiation during migration of dopaminergic progenitor cells to the olfactory bulb. J Neurosci 2001; 21:8505-13; PMID:11606639.
51. Thannickal TC, Lai YY, Siegel JM. Hypocretin (orexin) cell loss in Parkinson's disease. Brain 2007; 130:1586- 95; PMID:17491094; http://dx.doi.org/10.1093/brain/awm097.
52. Henderson JM, Carpenter K, Cartwright H, Halliday GM. Loss of thalamic intralaminar nuclei in progressive supranuclear palsy and Parkinson's disease: clinical and therapeutic implications. Brain 2000; 123:1410- 21; PMID:10869053; http://dx.doi.org/10.1093/brain/123.7.1410.
53. Jellinger KA. Lewy body-related alpha-synucleinopathy in the aged human brain. J Neural Transm 2004; 111:1219-35; PMID:15480835; http://dx.doi.org/10. 1007/s00702-004-0138-7.
54. Dickson DW, Braak H, Duda JE, Duyckaerts C, Gasser T, Halliday GM, et al. Neuropathological assessment of Parkinson's disease: refining the diagnostic criteria. Lancet Neurol 2009; 8:1150-7; PMID:19909913; http://dx.doi.org/10. 1016/S1474-4422(09)70238-8.
55. Harnois C, Marcotte G, Daigle M, Di Paolo T. Retinal dopamine sensitivity to MPP+ toxicity: electrophysiological and biochemical evaluation. Neurosci Lett 1989; 107:19-25; PMID:2616030; http://dx.doi.org/10.1016/0304-3940(89) 90784-2.
56. Cullen KM, Halliday GM. Neurofibrillary degeneration and cell loss in the nucleus basalis in comparison to cortical Alzheimer pathology. Neurobiol Aging 1998; 19:297-306; PMID:9733161; http://dx.doi.org/10.1016/S0197-4580(98)00066-9.
57. Nakano I, Hirano A. Parkinson's disease: neuron loss in the nucleus basalis without concomitant Alzheimer's disease. Ann Neurol 1984; 15:415-8; PMID:6732189; http://dx.doi.org/10.1002/ana.410150503.
58. Larsen KE, Fon EA, Hastings TG, Edwards RH, Sulzer D. Methamphetamine-induced degeneration of dopaminergic neurons involves autophagy and upregulation of dopamine synthesis. J Neurosci 2002; 22:8951-60; PMID:12388602.
59. Cubells JF, Rayport S, Rajendran G, Sulzer D. Methamphetamine neurotoxicity involves vacuolation of endocytic organelles and dopamine-dependent intracellular oxidative stress. J Neurosci 1994; 14:2260-71; PMID:8158268.
60. Mosharov EV, Larsen KE, Kanter E, Phillips KA, Wilson K, Schmitz Y, et al. Interplay between cytosolic dopamine, calcium, and alpha-synuclein causes selective death of substantia nigra neurons. Neuron 2009; 62:218-29; PMID:19409267; http://dx.doi.org/10.1016/j.neuron.2009.01.033.
61. Martinez-Vicente M, Talloczy Z, Kaushik S, Massey AC, Mazzulli J, Mosharov EV, et al. Dopaminemodified alpha-synuclein blocks chaperone-mediated autophagy. J Clin Invest 2008; 118:777-88; PMID:18172548.
62. Chen L, Ding Y, Cagniard B, Van Laar AD, Mortimer A, Chi W, et al. Unregulated cytosolic dopamine causes neurodegeneration associated with oxidative stress in mice. J Neurosci 2008; 28:425-33; PMID:18184785; http://dx.doi.org/10.1523/JNEUROSCI.3602-07.2008.
63. Sulzer D, Bogulavsky J, Larsen KE, Behr G, Karatekin E, Kleinman MH, et al. Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles. Proc Natl Acad Sci U S A 2000; 97:11869-74; PMID:11050221; http://dx.doi.org/10.1073/pnas.97.22.11869.
64. Sulzer D, Mosharov E, Talloczy Z, Zucca FA, Simon JD, Zecca L. Neuronal pigmented autophagic vacuoles: lipofuscin, neuromelanin, and ceroid as macroautophagic responses during aging and disease. J Neurochem 2008; 106:24-36; PMID:18384642; http://dx.doi.org/10.1111/j.1471-4159.2008.05385.x.
65. Braak H, Ghebremedhin E, Rüb U, Bratzke H, Del Tredici K. Stages in the development of Parkinson's disease- related pathology. Cell Tissue Res 2004; 318:121- 34; PMID:15338272; http://dx.doi.org/10.1007/s00441-004-0956-9.
66. Matsuda W, Furuta T, Nakamura KC, Hioki H, Fujiyama F, Arai R, et al. Single nigrostriatal dopaminergic neurons form widely spread and highly dense axonal arborizations in the neostriatum. J Neurosci 2009; 29:444-53; PMID:19144844; http://dx.doi.org/10.1523/JNEUROSCI.4029-08.2009.
67. Choi SW, Gerencser AA, Lee DW, Rajagopalan S, Nicholls DG, Andersen JK, et al. Intrinsic bioenergetic properties and stress sensitivity of dopaminergic synaptosomes. J Neurosci 2011; 31:4524- 34; PMID:21430153; http://dx.doi.org/10. 1523/JNEUROSCI.5817-10.2011.
68. Liang CL, Wang TT, Luby-Phelps K, German DC. Mitochondria mass is low in mouse substantia nigra dopamine neurons: implications for Parkinson's disease. Exp Neurol 2007; 203:370-80; PMID:17010972; http://dx.doi.org/10.1016/j. expneurol.2006.08.015.
69. Abeliovich A, Schmitz Y, Fariñas I, Choi-Lundberg D, Ho WH, Castillo PE, et al. Mice lacking alphasynuclein display functional deficits in the nigrostriatal dopamine system. Neuron 2000; 25:239-52; PMID:10707987; http://dx.doi.org/10.1016/S0896-6273(00)80886-7.
70. Larsen KE, Schmitz Y, Troyer MD, Mosharov E, Dietrich P, Quazi AZ, et al. Alpha-synuclein overexpression in PC12 and chromaffin cells impairs catecholamine release by interfering with a late step in exocytosis. J Neurosci 2006; 26:11915-22; PMID:17108165; http://dx.doi.org/10.1523/JNEUROSCI.3821-06. 2006.
71. Nemani VM, Lu W, Berge V, Nakamura K, Onoa B, Lee MK, et al. Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 2010; 65:66-79; PMID:20152114; http://dx.doi.org/10.1016/j.neuron.2009.12.023.
72. Nakamura K, Nemani VM, Azarbal F, Skibinski G, Levy JM, Egami K, et al. Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein alpha-synuclein. J Biol Chem 2011; 286:20710-26; PMID:21489994; http://dx.doi.org/10.1074/jbc.M110.213538.
73. Surmeier DJ, Guzman JN, Sanchez J, Schumacker PT. Physiological phenotype and vulnerability in Parkinson's disease. Cold Spring Harb Perspect Med 2012; 2:a009290; PMID:22762023.
74. Williams JT, North RA, Shefner SA, Nishi S, Egan TM. Membrane properties of rat locus coeruleus neurones. Neuroscience 1984; 13:137-56; PMID:6493483; http://dx.doi.org/10.1016/0306-4522(84)90265-3.
75. Aston-Jones G, Cohen JD. An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci 2005; 28:403-50; PMID:16022602; http://dx.doi.org/10.1146/annurev. neuro.28.061604.135709.
76. Travagli RA, Gillis RA, Rossiter CD, Vicini S. Glutamate and GABA-mediated synaptic currents in neurons of the rat dorsal motor nucleus of the vagus. Am J Physiol 1991; 260:G531-6; PMID:1672243.
77. Goldberg JA, Guzman JN, Estep CM, Ilijic E, Kondapalli J, Sanchez-Padilla J, et al. Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson's disease. Nat Neurosci 2012; 15:1414-21; PMID:22941107; http://dx.doi.org/10.1038/nn.3209.
78. McCann MJ, Rogers RC. Oxytocin excites gastricrelated neurones in rat dorsal vagal complex. J Physiol 1990; 428:95-108; PMID:2231433.
79. Chan JY, Chan SH. Passive electrical properties of spontaneously active neurons in the nucleus reticularis gigantocellularis of the cat. Neurosci Lett 1989; 97:169- 74; PMID:2919002; http://dx.doi.org/10.1016/0304-3940(89)90158-4.
80. Serafin M, Khateb A, Mühlethaler M. Electrophysiology and lucifer yellow injection of nucleus gigantocellularis neurones in an isolated and perfused guinea pig brain in vitro. Neurosci Lett 1990; 120:5-8; PMID:2293091; http://dx.doi.org/10.1016/0304-3940(90)90154-2.
81. Kang Y, Kitai ST. Electrophysiological properties of pedunculopontine neurons and their postsynaptic responses following stimulation of substantia nigra reticulata. Brain Res 1990; 535:79-95; PMID:2292031; http://dx.doi.org/10. 1016/0006-8993(90)91826-3.
82. Mao Y, Wang B, Kunze W. Characterization of myenteric sensory neurons in the mouse small intestine. J Neurophysiol 2006; 96:998-1010; PMID:16899648; http://dx.doi.org/10.1152/jn.00204.2006.
83. Rugiero F, Gola M, Kunze WA, Reynaud JC, Furness JB, Clerc N. Analysis of whole-cell currents by patch clamp of guinea-pig myenteric neurones in intact ganglia. J Physiol 2002; 538:447-63; PMID:11790812; http://dx.doi.org/10.1113/ jphysiol.2001.013051.
84. Clerc N, Furness JB, Bornstein JC, Kunze WA. Correlation of electrophysiological and morphological characteristics of myenteric neurons of the duodenum in the guinea-pig. Neuroscience 1998; 82:899-914; PMID:9483544; http://dx.doi.org/10.1016/S0306-4522(97)00318-7.
85. Foehring RC, Zhang XF, Lee JCF, Callaway JC. Endogenous calcium buffering capacity of substantia nigral dopamine neurons. J Neurophysiol 2009; 102:2326-33; PMID:19675297; http://dx.doi.org/10.1152/jn.00038.2009.
86. Schmidt H, Arendt O, Brown EB, Schwaller B, Eilers J. Parvalbumin is freely mobile in axons, somata and nuclei of cerebellar Purkinje neurones. J Neurochem 2007; 100:727-35; PMID:17263794; http://dx.doi.org/10.1111/j.1471- 4159.2006.04231.x.
87. Goldberg JA, Teagarden MA, Foehring RC, Wilson CJ. Nonequilibrium calcium dynamics regulate the autonomous firing pattern of rat striatal cholinergic interneurons. J Neurosci 2009; 29:8396- 407; PMID:19571130; http://dx.doi.org/ 10.1523/JNEUROSCI.5582-08.2009.
88. Clerc N, Furness JB, Li ZS, Bornstein JC, Kunze WA. Morphological and immunohistochemical identification of neurons and their targets in the guinea- pig duodenum. Neuroscience 1998; 86:679-94; PMID:9881879; http://dx.doi.org/10. 1016/S0306-4522(98)00025-6.
89. Tamura K, Ito H, Wade PR. Morphology, electrophysiology, and calbindin immunoreactivity of myenteric neurons in the guinea pig distal colon. J Comp Neurol 2001; 437:423-37; PMID:11503144; http://dx.doi.org/10.1002/cne.1293.
90. Gibb WRG. Melanin, tyrosine hydroxylase, calbindin and substance P in the human midbrain and substantia nigra in relation to nigrostriatal projections and differential neuronal susceptibility in Parkinson's disease. Brain Res 1992; 581:283-91; PMID:1382801; http://dx.doi.org/10.1016/0006-8993(92)90719-P.
91. Puopolo M, Raviola E, Bean BP. Roles of subthreshold calcium current and sodium current in spontaneous firing of mouse midbrain dopamine neurons. J Neurosci 2007; 27:645-56; PMID:17234596; http://dx.doi.org/10.1523/JNEUROSCI. 4341-06.2007.
92. Guzman JN, Sánchez-Padilla J, Chan CS, Surmeier DJ. Robust pacemaking in substantia nigra dopaminergic neurons. J Neurosci 2009; 29:11011- 9; PMID:19726659; http://dx.doi.org/10.1523/JNEUROSCI.2519-09.2009.
93. Putzier I, Kullmann PHM, Horn JP, Levitan ES. Cav1.3 channel voltage dependence, not Ca2+ selectivity, drives pacemaker activity and amplifies bursts in nigral dopamine neurons. J Neurosci 2009; 29:15414- 9; PMID:20007466; http://dx.doi.org/10.1523/JNEUROSCI.4742-09.2009.
94. Beal MF. Excitotoxicity and nitric oxide in Parkinson's disease pathogenesis. Ann Neurol 1998; 44(Suppl 1):S110-4; PMID:9749581.
95. Slivka A, Cohen G. Hydroxyl radical attack on dopamine. J Biol Chem 1985; 260:15466-72; PMID:2999117.
96. Nicholls DG. Spare respiratory capacity, oxidative stress and excitotoxicity. Biochem Soc Trans 2009; 37:1385- 8; PMID:19909281; http://dx.doi.org/10.1042/BST0371385.
97. Guzman JN, Sanchez-Padilla J, Wokosin D, Kondapalli J, Ilijic E, Schumacker PT, et al. Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature 2010; 468:696- 700; PMID:21068725; http://dx.doi.org/10.1038/nature09536.
98. Goldberg JA, Guzman JN, Estep CM, Ilijic E, Kondapalli J, Sanchez-Padilla J, et al. Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson's disease. Nat Neurosci 2012; 15:1414-21; PMID:22941107; http://dx.doi.org/10.1038/nn.3209.
99. Schapira AH. Mitochondria in the aetiology and pathogenesis of Parkinson's disease. Lancet Neurol 2008; 7:97-109; PMID:18093566; http://dx.doi.org/10.1016/S1474-4422(07)70327-7.
100. Bender A, Schwarzkopf RM, McMillan A, Krishnan KJ, Rieder G, Neumann M, et al. Dopaminergic midbrain neurons are the prime target for mitochondrial DNA deletions. J Neurol 2008; 255:1231-5; PMID:18604467; http://dx.doi.org/10.1007/ s00415-008-0892-9.
101. Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, et al. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 2006; 38:515-7; PMID:16604074; http://dx.doi.org/10.1038/ng1769.
102. Kraytsberg Y, Simon DK, Turnbull DM, Khrapko K. Do mtDNA deletions drive premature aging in mtDNA mutator mice? Aging Cell 2009; 8:502-6; PMID:19416127; http://dx.doi.org/10.1111/j.1474-9726.2009.00484.x.
103. Nath S, Goodwin J, Engelborghs Y, Pountney DL. Raised calcium promotes α-synuclein aggregate formation. Mol Cell Neurosci 2011; 46:516- 26; PMID:21145971; http://dx.doi.org/10.1016/j.mcn.2010.12.004.
104. Lloyd-Evans E, Platt FM. Lysosomal Ca(2+) homeostasis: role in pathogenesis of lysosomal storage diseases. Cell Calcium 2011; 50:200-5; PMID:21724254; http://dx.doi.org/10.1016/j.ceca.2011.03.010.
105. Pan T, Kondo S, Le W, Jankovic J. The role of autophagy- lysosome pathway in neurodegeneration associated with Parkinson's disease. Brain 2008; 131:1969-78; PMID:18187492; http://dx.doi.org/10.1093/brain/awm318.
106. Angot E, Steiner JA, Lema Tomé CM, Ekström P, Mattsson B, Björklund A, et al. Alpha-synuclein cell-to-cell transfer and seeding in grafted dopaminergic neurons in vivo. PLoS One 2012; 7:e39465; PMID:22737239; http://dx.doi.org/10.1371/journal.pone.0039465.
107. Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat Med 2008; 14:504-6; PMID:18391962; http://dx.doi.org/10.1038/nm1747.
108. Volpicelli-Daley LA, Luk KC, Patel TP, Tanik SA, Riddle DM, Stieber A, et al. Exogenous α-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 2011; 72:57- 71; PMID:21982369; http://dx.doi.org/10.1016/j.neuron.2011.08.033.
109. Mills IG, Urbé S, Clague MJ. Relationships between EEA1 binding partners and their role in endosome fusion. J Cell Sci 2001; 114:1959-65; PMID:11329382.
110. Savina A, Furlán M, Vidal M, Colombo MI. Exosome release is regulated by a calcium-dependent mechanism in K562 cells. J Biol Chem 2003; 278:20083- 90; PMID:12639953; http://dx.doi.org/10.1074/jbc.M301642200.
111. Barclay JW, Morgan A, Burgoyne RD. Calciumdependent regulation of exocytosis. Cell Calcium 2005; 38:343-53; PMID:16099500; http://dx.doi.org/10. 1016/j.ceca.2005.06.012.
112. Fauré J, Lachenal G, Court M, Hirrlinger J, Chatellard- Causse C, Blot B, et al. Exosomes are released by cultured cortical neurones. Mol Cell Neurosci 2006; 31:642-8; PMID:16446100; http://dx.doi.org/10.1016/j.mcn.2005.12. 003.
113. Emmanouilidou E, Melachroinou K, Roumeliotis T, Garbis SD, Ntzouni M, Margaritis LH, et al. Cell-produced alpha-synuclein is secreted in a calcium- dependent manner by exosomes and impacts neuronal survival. J Neurosci 2010; 30:6838-51; PMID:20484626; http://dx.doi.org/10.1523/JNEUROSCI.5699-09.2010.
114. Dittman J, Ryan TA. Molecular circuitry of endocytosis at nerve terminals. Annu Rev Cell Dev Biol 2009; 25:133-60; PMID:19575674; http://dx.doi.org/10.1146/annurev.cellbio.042308.113302.
115. Becker C, Jick SS, Meier CR. Use of antihypertensives and the risk of Parkinson disease. Neurology 2008; 70:1438-44; PMID:18256367; http://dx.doi.org/10.1212/01.wnl.0000303818.38960.44.
116. Ritz B, Rhodes SL, Qian L, Schernhammer E, Olsen JH, Friis S. L-type calcium channel blockers and Parkinson disease in Denmark. Ann Neurol 2010; 67:600-6; PMID:20437557.
117. Pasternak B, Svanström H, Nielsen NM, Fugger L, Melbye M, Hviid A. Use of calcium channel blockers and Parkinson's disease. Am J Epidemiol 2012; 175:627-35; PMID:22387374; http://dx.doi.org/10.1093/aje/kwr362.
118. Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, et al. Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 2012; 338:949- 53; PMID:23161999; http://dx.doi.org/10.1126/science.1227157.
119. Song YJ, Huang Y, Halliday GM. Clinical correlates of similar pathologies in parkinsonian syndromes. Mov Disord 2011; 26:499-506; PMID:21259341; http://dx.doi.org/10.1002/mds.23336.
120. Szego ÉM, Gerhardt E, Outeiro TF, Kermer P. Dopamine-depletion and increased α-synuclein load induce degeneration of cortical cholinergic fibers in mice. J Neurol Sci 2011; 310:90-55; PMID:21774947; http://dx.doi.org/10.1016/j.jns.2011.06.048.